Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Biomaterials to enhance adoptive cell therapy

Nature Reviews Bioengineering (2024)Cite this article

Subjects

Abstract

Adoptive cell therapy (ACT) harnesses the capabilities of immune cells to fight complex diseases such as cancer. Treatment with adoptive transfer of engineered cells has led to impressive remission rates in patients with haematological malignancies. Despite these advances, ACT remains limited by treatment-related adverse effects, scaling challenges, limited access of immune cells to some disease sites, and the immunosuppressive milieu of solid tumours. New biomaterials technologies for improving cell-manufacturing techniques and the controlled delivery of engineered cells into the body are proving capable of overcoming these limitations. Tunable biomaterials can be used to mitigate the high cost and time-intensive manufacturing of ACT. Further, numerous biomaterials platforms, ranging from nanoparticles to hydrogels, have been engineered to enable spatial and temporal control of the expansion and release of engineered cells while limiting their propensity to develop exhaustion phenotypes. This Review describes the fundamental roles of biomaterials as both manufacturing platforms and delivery vehicles for enhancing ACT, and also highlights current and future applications of these materials-based approaches that could lead to improved therapeutic outcomes.

Key points

  • Biomaterials have important applications in the production, engineering and delivery of multiple immune-cell types used for adoptive cell therapy (ACT).

  • Three-dimensional scaffolds, artificial antigen-presenting cells and in vivo production are expected to improve the reliability and scalability of ACT, as well as reducing its cost and production time.

  • Localized delivery and slow-release formulations that incorporate stimulatory cofactors reduce the risks associated with currently approved ACTs.

  • The applications of biomaterials-enabled ACT could be expanded to non-oncological settings such as autoimmune disorders and infectious diseases.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Biomaterials and the development of adoptive cell therapies.
Fig. 2: Current challenges in adoptive cell therapy that can be addressed using biomaterials.
Fig. 3: Uses of biomaterials in the manufacture of adoptive cell therapy.
Fig. 4: Applications of biomaterials in the delivery of adoptive cell therapy.

Similar content being viewed by others

References

  1. June, C. H., Riddell, S. R. & Schumacher, T. N. Adoptive cellular therapy: a race to the finish line. Sci. Transl. Med. 7, 280ps7 (2015).

    Article  Google Scholar 

  2. Farkona, S., Diamandis, E. P. & Blasutig, I. M. Cancer immunotherapy: the beginning of the end of cancer? BMC Med. 14, 73 (2016).

    Article  Google Scholar 

  3. Hawkins, R. E. et al. Development of adoptive cell therapy for cancer: a clinical perspective. Hum. Gene Ther. 21, 665–672 (2010).

    Article  Google Scholar 

  4. Rohaan, M. W., Wilgenhof, S. & Haanen, J. B. A. G. Adoptive cellular therapies: the current landscape. Virchows Arch. 474, 449–461 (2019).

    Article  Google Scholar 

  5. Schuster, S. J. et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N. Engl. J. Med. 377, 2545–2554 (2017).

    Article  Google Scholar 

  6. Maude, S. L. et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Engl. J. Med. 371, 1507–1517 (2014).

    Article  Google Scholar 

  7. Lee, D. W. et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 385, 517–528 (2015).

    Article  Google Scholar 

  8. Davila, M. L. et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci. Transl. Med. 6, 224ra25 (2014).

    Article  Google Scholar 

  9. Kalos, M. et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci. Transl. Med. 3, 95ra73 (2011).

    Article  Google Scholar 

  10. Porter, D. L., Levine, B. L., Kalos, M., Bagg, A. & June, C. H. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N. Engl. J. Med. 365, 725–733 (2011).

    Article  Google Scholar 

  11. Labanieh, L. & Mackall, C. L. CAR immune cells: design principles, resistance and the next generation. Nature 614, 635–648 (2023).

    Article  Google Scholar 

  12. Isser, A., Livingston, N. K. & Schneck, J. P. Biomaterials to enhance antigen-specific T cell expansion for cancer immunotherapy. Biomaterials 268, 120584 (2021).

    Article  Google Scholar 

  13. Vormittag, P., Gunn, R., Ghorashian, S. & Veraitch, F. S. A guide to manufacturing CAR T cell therapies. Curr. Opin. Biotechnol. 53, 164–181 (2018).

    Article  Google Scholar 

  14. FDA. Approved cellular and gene therapy products. FDA www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products (2023).

  15. Stephenson, M. & Grayson, W. Recent advances in bioreactors for cell-based therapies. F1000Res 7, 517 (2018).

    Article  Google Scholar 

  16. Tyagarajan, S., Spencer, T. & Smith, J. Optimizing CAR-T cell manufacturing processes during pivotal clinical trials. Mol. Ther. Methods Clin. Dev. 16, 136–144 (2020).

    Article  Google Scholar 

  17. Tie, Y., Tang, F., Wei, Y. & Wei, X. Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets. J. Hematol. Oncol. 15, 61 (2022).

    Article  Google Scholar 

  18. Lyman, G. H., Nguyen, A., Snyder, S., Gitlin, M. & Chung, K. C. Economic evaluation of chimeric antigen receptor T-cell therapy by site of care among patients with relapsed or refractory large B-cell lymphoma. JAMA Netw. Open. 3, e202072 (2020).

    Article  Google Scholar 

  19. Fitzgerald, J. C. et al. Cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia. Crit. Care Med. 45, e124 (2017).

    Article  Google Scholar 

  20. Gardner, R. et al. Decreased rates of severe CRS seen with early intervention strategies for CD19 CAR-T cell toxicity management. Blood 128, 586 (2016).

    Article  Google Scholar 

  21. Neill, L., Rees, J. & Roddie, C. Neurotoxicity — CAR T-cell therapy: what the neurologist needs to know. Pract. Neurol. 20, 285–293 (2020).

    Article  Google Scholar 

  22. Davila, M. L. & Sadelain, M. Biology and clinical application of CAR T cells for B cell malignancies. Int. J. Hematol. 104, 6–17 (2016).

    Article  Google Scholar 

  23. Flugel, C. L. et al. Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours. Nat. Rev. Clin. Oncol. 20, 49–62 (2023).

    Article  Google Scholar 

  24. Huang, M., Deng, J., Gao, L. & Zhou, J. Innovative strategies to advance CAR T cell therapy for solid tumors. Am. J. Cancer Res. 10, 1979–1992 (2020).

    Google Scholar 

  25. Akbari, P., Huijbers, E. J. M., Themeli, M., Griffioen, A. W. & van Beijnum, J. R. The tumor vasculature: an attractive CAR T cell target in solid tumors. Angiogenesis 22, 473–475 (2019).

    Article  Google Scholar 

  26. Marofi, F. et al. CAR T cells in solid tumors: challenges and opportunities. Stem Cell Res. Ther. 12, 81 (2021).

    Article  Google Scholar 

  27. Moon, E. K. et al. Multifactorial T-cell hypofunction that is reversible can limit the efficacy of chimeric antigen receptor–transduced human T cells in solid tumors. Clin. Cancer Res. 20, 4262–4273 (2014).

    Article  Google Scholar 

  28. Wang, D. et al. Extracellular matrix viscosity reprogramming by in situ Au bioreactor-boosted microwave genetics disables tumor escape in CAR-T immunotherapy. ACS Nano 17, 5503–5516 (2023).

    Article  Google Scholar 

  29. Xia, Y. et al. Engineering macrophages for cancer immunotherapy and drug delivery. Adv. Mater. 32, 2002054 (2020).

    Article  Google Scholar 

  30. Xu, S. et al. The role of collagen in cancer: from bench to bedside. J. Transl. Med. 17, 309 (2019).

    Article  Google Scholar 

  31. Jiang, J. & Ahuja, S. Addressing patient to patient variability for autologous CAR T therapies. J. Pharm. Sci. 110, 1871–1876 (2021).

    Article  Google Scholar 

  32. Abdeen, A. A. & Saha, K. Manufacturing cell therapies using engineered biomaterials. Trends Biotechnol. 35, 971–982 (2017).

    Article  Google Scholar 

  33. Chen, R. et al. Biomaterial-assisted scalable cell production for cell therapy. Biomaterials 230, 119627 (2020).

    Article  Google Scholar 

  34. Chen, Y., Pal, S. & Hu, Q. Recent advances in biomaterial-assisted cell therapy. J. Mater. Chem. B 10, 7222–7238 (2022).

    Article  Google Scholar 

  35. Moysidou, C.-M., Barberio, C. & Owens, R. M. Advances in engineering human tissue models. Front. Bioeng. Biotechnol. 8, 620962 (2021).

    Article  Google Scholar 

  36. Correa, S. et al. Translational applications of hydrogels. Chem. Rev. 121, 11385–11457 (2021).

    Article  Google Scholar 

  37. Pek, Y. S., Wan, A. C. A. & Ying, J. Y. The effect of matrix stiffness on mesenchymal stem cell differentiation in a 3D thixotropic gel. Biomaterials 31, 385–391 (2010).

    Article  Google Scholar 

  38. Vasudevan, J., Jiang, K., Fernandez, Javier, G. & Lim, C. T. Extracellular matrix mechanobiology in cancer cell migration. Acta Biomater. 163, 351–364 (2023).

    Article  Google Scholar 

  39. Wells, R. G. The role of matrix stiffness in regulating cell behavior. Hepatology 47, 1394–1400 (2008).

    Article  Google Scholar 

  40. Sunyer, R. & Trepat, X. Durotaxis. Curr. Biol. 30, R383–R387 (2020).

    Article  Google Scholar 

  41. Shellard, A. & Mayor, R. Durotaxis: the hard path from in vitro to in vivo. Dev. Cell 56, 227–239 (2021).

    Article  Google Scholar 

  42. Grosskopf, A. K. et al. Injectable supramolecular polymer–nanoparticle hydrogels enhance human mesenchymal stem cell delivery. Bioeng. Transl. Med. 5, e10147 (2020).

    Article  Google Scholar 

  43. Majedi, F. S. et al. T-cell activation is modulated by the 3D mechanical microenvironment. Biomaterials 252, 120058 (2020).

    Article  Google Scholar 

  44. Chin, M. H., Norman, M. D., Gentleman, E., Coppens, M.-O. & Day, R. M. A hydrogel-integrated culture device to interrogate T cell activation with physicochemical cues. ACS Appl. Mater. Interfaces 12, 47355–47367 (2020).

    Article  Google Scholar 

  45. Pruitt, H. C. et al. Collagen VI deposition mediates stromal T cell trapping through inhibition of T cell motility in the prostate tumor microenvironment. Matrix Biol. 121, 90–104 (2023).

    Article  Google Scholar 

  46. Krummel, M. F., Bartumeus, F. & Gérard, A. T cell migration, search strategies and mechanisms. Nat. Rev. Immunol. 16, 193–201 (2016).

    Article  Google Scholar 

  47. Hickey, J. W. et al. Engineering an artificial T-cell stimulating matrix for immunotherapy. Adv. Mater. 31, 1807359 (2019). This work combines biophysical and biochemical cues to develop an artificial hyaluronic-acid-based T cell stimulating matrix for the expansion of antigen-specific CD8+ T cells.

    Article  Google Scholar 

  48. Adu-Berchie, K. et al. Generation of functionally distinct T-cell populations by altering the viscoelasticity of their extracellular matrix. Nat. Biomed. Eng. 7, 1374–1391 (2023).

    Article  Google Scholar 

  49. Oyen, M. Mechanical characterisation of hydrogel materials. Int. Mater. Rev. 59, 44–59 (2014).

    Article  Google Scholar 

  50. Li, J. & Mooney, D. J. Designing hydrogels for controlled drug delivery. Nat. Rev. Mater. 1, 16071 (2016).

    Article  Google Scholar 

  51. Grosskopf, A. K. et al. Delivery of CAR-T cells in a transient injectable stimulatory hydrogel niche improves treatment of solid tumors. Sci. Adv. 8, eabn8264 (2022). This paper describes an injectable hydrogel system for the co-delivery of B7H3 CAR T cells and IL-15, which promotes CAR T expansion and activation, for the treatment of solid tumours in immunodeficient mice.

    Article  Google Scholar 

  52. Fan, C. & Wang, D.-A. Macroporous hydrogel scaffolds for three-dimensional cell culture and tissue engineering. Tissue Eng. Part. B Rev. 23, 451–461 (2017).

    Article  Google Scholar 

  53. Ikada, Y. Challenges in tissue engineering. J. R. Soc. Interface 3, 589–601 (2006).

    Article  Google Scholar 

  54. Del Río, E. P. et al. CCL21-loaded 3D hydrogels for T cell expansion and differentiation. Biomaterials 259, 120313 (2020).

    Article  Google Scholar 

  55. Monette, A., Ceccaldi, C., Assaad, E., Lerouge, S. & Lapointe, R. Chitosan thermogels for local expansion and delivery of tumor-specific T lymphocytes towards enhanced cancer immunotherapies. Biomaterials 75, 237–249 (2016).

    Article  Google Scholar 

  56. Podhorská, B. et al. Revealing the true morphological structure of macroporous soft hydrogels for tissue engineering. Appl. Sci. 10, 6672 (2020).

    Article  Google Scholar 

  57. Liu, Y. et al. Cytokine conjugation to enhance T cell therapy. Proc. Natl Acad. Sci. 120, e2213222120 (2023).

    Article  Google Scholar 

  58. Weiden, J. et al. Injectable biomimetic hydrogels as tools for efficient T cell expansion and delivery. Front. Immunol. 9, 2798 (2018).

    Article  Google Scholar 

  59. Klouda, L. Thermoresponsive hydrogels in biomedical applications: a seven-year update. Eur. J. Pharm. Biopharm. 97, 338–349 (2015).

    Article  Google Scholar 

  60. Agarwalla, P. et al. Scaffold-mediated static transduction of T cells for CAR-T cell therapy. Adv. Healthc. Mater. 9, 2000275 (2020).

    Article  Google Scholar 

  61. VanBlunk, M., Srikanth, V., Pandit, S. S., Kuznetsov, A. V. & Brudno, Y. Absorption rate governs cell transduction in dry macroporous scaffolds. Biomater. Sci. 11, 2372–2382 (2023).

    Article  Google Scholar 

  62. Jie, J., Mao, D., Cao, J., Feng, P. & Yang, P. Customized multifunctional peptide hydrogel scaffolds for CAR-T-cell rapid proliferation and solid tumor immunotherapy. ACS Appl. Mater. Interfaces 14, 37514–37527 (2022).

    Article  Google Scholar 

  63. Agarwalla, P. et al. Bioinstructive implantable scaffolds for rapid in vivo manufacture and release of CAR-T cells. Nat. Biotechnol. 40, 1250–1258 (2022). This work describes an implantable alginate scaffold that carries out both engineering and delivery of CD19 CAR T cells, used for the treatment of a xenograft lymphoma model.

    Article  Google Scholar 

  64. Rhodes, K. R. & Green, J. J. Nanoscale artificial antigen presenting cells for cancer immunotherapy. Mol. Immunol. 98, 13–18 (2018).

    Article  Google Scholar 

  65. Wauters, A. C. et al. Artificial antigen-presenting cell topology dictates T cell activation. ACS Nano 16, 15072–15085 (2022).

    Article  Google Scholar 

  66. Cheung, A. S., Zhang, D. K., Koshy, S. T. & Mooney, D. J. Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary T cells. Nat. Biotechnol. 36, 160–169 (2018). This paper reports superior ex vivo expansion of murine and human T cells achieved by artificial antigen-presenting cells based on mesoporous silica nanorods versus commercial expansion methods.

    Article  Google Scholar 

  67. Zhang, D. K. et al. Enhancing CAR-T cell functionality in a patient-specific manner. Nat. Commun. 14, 506 (2023).

    Article  Google Scholar 

  68. Olden, B. R. et al. Cell-templated silica microparticles with supported lipid bilayers as artificial antigen-presenting cells for T cell activation. Adv. Healthc. Mater. 8, 1801188 (2019).

    Article  Google Scholar 

  69. Hammink, R. et al. Semiflexible immunobrushes induce enhanced T cell activation and expansion. ACS Appl. Mater. Interfaces 13, 16007–16018 (2021).

    Article  Google Scholar 

  70. Bomb, K. et al. Cell therapy biomanufacturing: integrating biomaterial and flow-based membrane technologies for production of engineered T-cells. Adv. Mater. Technol. 8, 2201155 (2023).

    Article  Google Scholar 

  71. Higuchi, A., Ling, Q.-D., Chang, Y., Hsu, S.-T. & Umezawa, A. Physical cues of biomaterials guide stem cell differentiation fate. Chem. Rev. 113, 3297–3328 (2013).

    Article  Google Scholar 

  72. Nianias, A. & Themeli, M. Induced pluripotent stem cell (iPSC)–derived lymphocytes for adoptive cell immunotherapy: recent advances and challenges. Curr. Hematol. Malig. Rep. 14, 261–268 (2019).

    Article  Google Scholar 

  73. Smerchansky, M. E. & Kinney, M. A. Engineered multicellular niches for pluripotent stem cell–derived immunotherapy. Curr. Opin. Biomed. Eng. 16, 19–26 (2020).

    Article  Google Scholar 

  74. Fathi, E., Farahzadi, R. & Valipour, B. Alginate/gelatin encapsulation promotes NK cells differentiation potential of bone marrow resident C-kit+ hematopoietic stem cells. Int. J. Biol. Macromol. 177, 317–327 (2021).

    Article  Google Scholar 

  75. Wang, Z. et al. 3D-organoid culture supports differentiation of human CAR+ iPSCs into highly functional CAR T cells. Cell Stem Cell 29, 515–527 (2022).

    Article  Google Scholar 

  76. Billingsley, M. M. et al. Ionizable lipid nanoparticle-mediated mRNA delivery for human CAR T cell engineering. Nano Lett. 20, 1578–1589 (2020).

    Article  Google Scholar 

  77. Billingsley, M. M. et al. Orthogonal design of experiments for optimization of lipid nanoparticles for mRNA engineering of CAR T cells. Nano Lett. 22, 533–542 (2021).

    Article  Google Scholar 

  78. Ye, Z. et al. In vitro engineering chimeric antigen receptor macrophages and T cells by lipid nanoparticle-mediated mRNA delivery. ACS Biomater. Sci. Eng. 8, 722–733 (2022).

    Article  Google Scholar 

  79. Patel, S. K. et al. Hydroxycholesterol substitution in ionizable lipid nanoparticles for mRNA delivery to T cells. J. Control. Rel. 347, 521–532 (2022).

    Article  Google Scholar 

  80. Seow, Y. & Wood, M. J. Biological gene delivery vehicles: beyond viral vectors. Mol. Ther. 17, 767–777 (2009).

    Article  Google Scholar 

  81. Pinto, I. S., Cordeiro, R. A. & Faneca, H. Polymer- and lipid-based gene delivery technology for CAR T cell therapy. J. Control. Rel. 353, 196–215 (2023).

    Article  Google Scholar 

  82. Raes, L., De Smedt, S. C., Raemdonck, K. & Braeckmans, K. Non-viral transfection technologies for next-generation therapeutic T cell engineering. Biotechnol. Adv. 49, 107760 (2021).

    Article  Google Scholar 

  83. Smith, T. T. et al. In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers. Nat. Nanotechnol. 12, 813–820 (2017).

    Article  Google Scholar 

  84. Mangraviti, A. et al. Polymeric nanoparticles for nonviral gene therapy extend brain tumor survival in vivo. ACS Nano 9, 1236–1249 (2015).

    Article  Google Scholar 

  85. Kim, K.-S. et al. Multifunctional nanoparticles for genetic engineering and bioimaging of natural killer (NK) cell therapeutics. Biomaterials 221, 119418 (2019).

    Article  Google Scholar 

  86. Moffett, H. F. et al. Hit-and-run programming of therapeutic cytoreagents using mRNA nanocarriers. Nat. Commun. 8, 389 (2017).

    Article  Google Scholar 

  87. Yu, Q. et al. Self-assembled nanoparticles prepared from low-molecular-weight PEI and low-generation PAMAM for EGFRvIII-chimeric antigen receptor gene loading and T-cell transient modification. Int. J. Nanomed. 15, 483–495 (2020).

    Article  Google Scholar 

  88. Olden, B. R., Cheng, Y., Yu, J. L. & Pun, S. H. Cationic polymers for non-viral gene delivery to human T cells. J. Control. Rel. 282, 140–147 (2018).

    Article  Google Scholar 

  89. Xie, Y. et al. Targeted delivery of siRNA to activated T cells via transferrin–polyethylenimine (Tf-PEI) as a potential therapy of asthma. J. Control. Rel. 229, 120–129 (2016).

    Article  Google Scholar 

  90. Raup, A. et al. Influence of polyplex formation on the performance of star-shaped polycationic transfection agents for mammalian cells. Polymers 8, 224 (2016).

    Article  Google Scholar 

  91. Olden, B. R., Cheng, E., Cheng, Y. & Pun, S. H. Identifying key barriers in cationic polymer gene delivery to human T cells. Biomater. Sci. 7, 789–797 (2019).

    Article  Google Scholar 

  92. Villanueva, M. T. Macrophages get a CAR. Nat. Rev. Cancer 20, 300 (2020).

    Article  Google Scholar 

  93. Rurik, J. G. et al. CAR T cells produced in vivo to treat cardiac injury. Science 375, 91–96 (2022). This report describes the use of CD5-targeted lipid nanoparticles to transform endogenous T cells into therapeutic anti-activated fibroblast CAR T cells in vivo.

    Article  Google Scholar 

  94. Wu, X. et al. Injectable scaffolds for in vivo programmed macrophages manufacture and postoperative cancer immunotherapy. Adv. Funct. Mater. 33, 2300058 (2023).

    Article  Google Scholar 

  95. Hu, D. et al. Improving safety of cancer immunotherapy via delivery technology. Biomaterials 265, 120407 (2021).

    Article  Google Scholar 

  96. Xie, Y.-Q., Wei, L. & Tang, L. Immunoengineering with biomaterials for enhanced cancer immunotherapy. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 10, e1506 (2018).

    Article  Google Scholar 

  97. Balagopal, S., Sasaki, K., Kaur, P., Nikolaidi, M. & Ishihara, J. Emerging approaches for preventing cytokine release syndrome in CAR-T cell therapy. J. Mater. Chem. B 10, 7491–7511 (2022).

    Article  Google Scholar 

  98. Jons, C. K. et al. Yield-stress and creep control depot formation and persistence of injectable hydrogels following subcutaneous administration. Adv. Funct. Mater. 32, 2203402 (2022).

    Article  Google Scholar 

  99. Chan, G. & Mooney, D. J. Ca2+ released from calcium alginate gels can promote inflammatory responses in vitro and in vivo. Acta Biomater. 9, 9281–9291 (2013).

    Article  Google Scholar 

  100. Dong, C. & Lv, Y. Application of collagen scaffold in tissue engineering: recent advances and new perspectives. Polymers 8, 42 (2016).

    Article  Google Scholar 

  101. Papakonstantinou, E., Roth, M. & Karakiulakis, G. Hyaluronic acid: a key molecule in skin aging. Dermato-endocrinology 4, 253–258 (2012).

    Article  Google Scholar 

  102. Reid, B. et al. PEG hydrogel degradation and the role of the surrounding tissue environment. J. Tissue Eng. Regen. Med. 9, 315–318 (2015).

    Article  Google Scholar 

  103. Mhaidly, R. & Verhoeyen, E. Humanized mice are precious tools for preclinical evaluation of CAR T and CAR NK cell therapies. Cancers 12, 1915 (2020).

    Article  Google Scholar 

  104. Stein, A. M. et al. Tisagenlecleucel model-based cellular kinetic analysis of chimeric antigen receptor-T cells. CPT Pharmacomet. Syst. Pharmacol. 8, 285–295 (2019).

    Article  Google Scholar 

  105. Mueller, K. T. et al. Cellular kinetics of CTL019 in relapsed/refractory B-cell acute lymphoblastic leukemia and chronic lymphocytic leukemia. Blood 130, 2317–2325 (2017).

    Article  Google Scholar 

  106. Silveira, C. R. F. et al. Cytokines as an important player in the context of CAR-T cell therapy for cancer: their role in tumor immunomodulation, manufacture, and clinical implications. Front. Immunol. 13, 947648 (2022).

    Article  Google Scholar 

  107. Kim, G. B., Riley, J. L. & Levine, B. L. Engineering T cells to survive and thrive in the hostile tumor microenvironment. Curr. Opin. Biomed. Eng. 21, 100360 (2022).

    Article  Google Scholar 

  108. Briukhovetska, D. et al. Interleukins in cancer: from biology to therapy. Nat. Rev. Cancer 21, 481–499 (2021).

    Article  Google Scholar 

  109. Waldmann, T. A. Cytokines in cancer immunotherapy. Cold Spring Harb. Perspect. Biol. 10, a028472 (2018).

    Article  Google Scholar 

  110. Agarwal, Y. et al. Intratumourally injected alum-tethered cytokines elicit potent and safer local and systemic anticancer immunity. Nat. Biomed. Eng. 6, 129–143 (2022).

    Article  Google Scholar 

  111. Zheng, Y. et al. In vivo targeting of adoptively transferred T-cells with antibody-and cytokine-conjugated liposomes. J. Control. Rel. 172, 426–435 (2013).

    Article  Google Scholar 

  112. Cieri, N. et al. IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors. Blood 121, 573–584 (2013).

    Article  Google Scholar 

  113. Kim, H. S. et al. Dendritic cell-mimicking scaffolds for ex vivo T cell expansion. Bioact. Mater. 21, 241–252 (2023).

    Google Scholar 

  114. Lin, G. H. et al. Evaluating the cellular targets of anti-4-1BB agonist antibody during immunotherapy of a pre-established tumor in mice. PLoS ONE 5, e11003 (2010).

    Article  Google Scholar 

  115. Ishikawa, T. et al. Cytotoxic T lymphocyte-associated antigen 4 inhibition increases the antitumor activity of adoptive T-cell therapy when carried out with naive rather than differentiated T cells. Oncol. Rep. 33, 2545–2552 (2015).

    Article  Google Scholar 

  116. Le Mercier, I., Lines, J. L. & Noelle, R. J. Beyond CTLA-4 and PD-1, the generation Z of negative checkpoint regulators. Front. Immunol. 6, 418 (2015).

    Article  Google Scholar 

  117. Hu, Q. et al. Inhibition of post-surgery tumour recurrence via a hydrogel releasing CAR-T cells and anti-PDL1-conjugated platelets. Nat. Biomed. Eng. 5, 1038–1047 (2021).

    Article  Google Scholar 

  118. Barber, G. N. STING-dependent cytosolic DNA sensing pathways. Trends Immunol. 35, 88–93 (2014).

    Article  Google Scholar 

  119. Xu, N. et al. STING agonist promotes CAR T cell trafficking and persistence in breast cancer. J. Exp. Med. 218, e20200844 (2021).

    Article  Google Scholar 

  120. Smith, T. T. et al. Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors. J. Clin. Invest. 127, 2176–2191 (2017).

    Article  Google Scholar 

  121. Liu, Y. et al. A tetramethylpyrazine releasing hydrogel can potentiate CAR-T cell therapy against triple negative breast cancer by reprogramming tumor vasculatures. Fundament. Res. https://doi.org/10.1016/j.fmre.2023.05.016 (2023).

  122. Huang, Y. et al. Dual-mechanism based CTLs infiltration enhancement initiated by Nano-sapper potentiates immunotherapy against immune-excluded tumors. Nat. Commun. 11, 622 (2020).

    Article  Google Scholar 

  123. Tsao, C.-T. et al. Thermoreversible poly (ethylene glycol)-G-chitosan hydrogel as a therapeutic T lymphocyte depot for localized glioblastoma immunotherapy. Biomacromolecules 15, 2656–2662 (2014).

    Article  Google Scholar 

  124. Wang, K. et al. GD2-specific CAR T cells encapsulated in an injectable hydrogel control retinoblastoma and preserve vision. Nat. Cancer 1, 990–997 (2020).

    Article  Google Scholar 

  125. Li, H. et al. Scattered seeding of CAR T cells in solid tumors augments anticancer efficacy. Natl Sci. Rev. 9, nwab172 (2022). This paper describes the use of a porous microneedle patch to deliver CAR T cells into a surgical resection site in an orthotopic pancreatic tumour model.

    Article  MathSciNet  Google Scholar 

  126. Stephan, S. B. et al. Biopolymer implants enhance the efficacy of adoptive T-cell therapy. Nat. Biotechnol. 33, 97–101 (2015).

    Article  Google Scholar 

  127. Majedi, F. S. et al. Systemic enhancement of antitumour immunity by peritumourally implanted immunomodulatory macroporous scaffolds. Nat. Biomed. Eng. 7, 56–71 (2022).

    Article  Google Scholar 

  128. Chao, Y. et al. Metformin-containing hydrogel scaffold to augment CAR-T therapy against post-surgical solid tumors. Biomaterials 295, 122052 (2023).

    Article  Google Scholar 

  129. Ahn, Y. H. et al. A three-dimensional hyaluronic acid-based niche enhances the therapeutic efficacy of human natural killer cell-based cancer immunotherapy. Biomaterials 247, 119960 (2020).

    Article  Google Scholar 

  130. Leach, D. G., Young, S. & Hartgerink, J. D. Advances in immunotherapy delivery from implantable and injectable biomaterials. Acta Biomater. 88, 15–31 (2019).

    Article  Google Scholar 

  131. Jeon, O. et al. Mechanical properties and degradation behaviors of hyaluronic acid hydrogels cross-linked at various cross-linking densities. Carbohydr. Polym. 70, 251–257 (2007).

    Article  Google Scholar 

  132. Atik, A. F. et al. Hyaluronic acid based low viscosity hydrogel as a novel carrier for convection enhanced delivery of CAR T cells. J. Clin. Neurosci. 56, 163–168 (2018).

    Article  Google Scholar 

  133. Kim, D. et al. NK cells encapsulated in micro/macropore-forming hydrogels via 3D bioprinting for tumor immunotherapy. Biomater. Res. 27, 60 (2023).

    Article  Google Scholar 

  134. Ogunnaike, E. A. et al. Fibrin gel enhances the antitumor effects of chimeric antigen receptor T cells in glioblastoma. Sci. Adv. 7, eabg5841 (2021).

    Article  Google Scholar 

  135. Uslu, U. et al. Chimeric antigen receptor T cells as adjuvant therapy for unresectable adenocarcinoma. Sci. Adv. 9, eade2526 (2023).

    Article  Google Scholar 

  136. Li, J. et al. Implantable and injectable biomaterial scaffolds for cancer immunotherapy. Front. Bioeng. Biotechnol. 8, 612950 (2020).

    Article  Google Scholar 

  137. Lee, J. H. Injectable hydrogels delivering therapeutic agents for disease treatment and tissue engineering. Biomater. Res. 22, 27 (2018).

    Article  Google Scholar 

  138. Zhou, W. et al. Injectable and photocurable CAR-T cell formulation enhances the anti-tumor activity to melanoma in mice. Biomaterials 291, 121872 (2022).

    Article  Google Scholar 

  139. Yang, P. et al. Engineering dendritic-cell-based vaccines and PD-1 blockade in self-assembled peptide nanofibrous hydrogel to amplify antitumor T-cell immunity. Nano Lett. 18, 4377–4385 (2018).

    Article  Google Scholar 

  140. Jain, E., Hill, L., Canning, E., Sell, S. A. & Zustiak, S. P. Control of gelation, degradation and physical properties of polyethylene glycol hydrogels through the chemical and physical identity of the crosslinker. J. Mater. Chem. B 5, 2679–2691 (2017).

    Article  Google Scholar 

  141. Bashir, S. et al. Fundamental concepts of hydrogels: synthesis, properties, and their applications. Polymers 12, 2702 (2020).

    Article  Google Scholar 

  142. Bhatta, R., Han, J., Liu, Y., Bo, Y. & Wang, H. T cell-responsive macroporous hydrogels for in situ T cell expansion and enhanced antitumor efficacy. Biomaterials 293, 121972 (2022).

    Article  Google Scholar 

  143. Chen, C. et al. Intracavity generation of glioma stem cell-specific CAR macrophages primes locoregional immunity for postoperative glioblastoma therapy. Sci. Transl. Med. 14, eabn1128 (2022). This paper describes an injectable hydrogel that delivers CAR genetic material to create CAR macrophages in the cavity left by surgical removal of a tumour.

    Article  Google Scholar 

  144. Arjomandnejad, M., Kopec, A. L. & Keeler, A. M. CAR-T regulatory (CAR-Treg) cells: engineering and applications. Biomedicines 10, 287 (2022).

    Article  Google Scholar 

  145. Shannon, R. S., Ben-Akiva, E. & Green, J. Approaches towards biomaterial-mediated gene editing for cancer immunotherapy. Biomater. Sci. 10, 6675–6687 (2022).

    Article  Google Scholar 

  146. Balakrishnan, P. B. & Sweeney, E. E. Nanoparticles for enhanced adoptive T cell therapies and future perspectives for CNS tumors. Front. Immunol. 12, 600659 (2021).

    Article  Google Scholar 

  147. Gao, A. et al. Overview of recent advances in liposomal nanoparticle-based cancer immunotherapy. Acta Pharmacol. Sin. 40, 1129–1137 (2019).

    Article  Google Scholar 

  148. Zheng, Y., Tang, L., Mabardi, L., Kumari, S. & Irvine, D. J. Enhancing adoptive cell therapy of cancer through targeted delivery of small-molecule immunomodulators to internalizing or noninternalizing receptors. ACS Nano 11, 3089–3100 (2017).

    Article  Google Scholar 

  149. Zhang, F. et al. Nanoparticles that reshape the tumor milieu create a therapeutic window for effective T-cell therapy in solid malignancies. Cancer Res. 78, 3718–3730 (2018).

    Article  Google Scholar 

  150. Tang, L. et al. Enhancing T cell therapy through TCR-signaling-responsive nanoparticle drug delivery. Nat. Biotechnol. 36, 707–716 (2018).

    Article  Google Scholar 

  151. Luo, Y. et al. IL-12 nanochaperone-engineered CAR T cell for robust tumor-immunotherapy. Biomaterials 281, 121341 (2022).

    Article  Google Scholar 

  152. Tang, X. et al. Magnetic–acoustic sequentially actuated CAR T cell microrobots for precision navigation and in situ antitumor immunoactivation. Adv. Mater. 35, 2211509 (2023).

    Article  Google Scholar 

  153. Oroojalian, F., Beygi, M., Baradaran, B., Mokhtarzadeh, A. & Shahbazi, M.-A. Immune cell membrane-coated biomimetic nanoparticles for targeted cancer therapy. Small 17, 2006484 (2021).

    Article  Google Scholar 

  154. Ma, L. et al. Enhanced CAR–T cell activity against solid tumors by vaccine boosting through the chimeric receptor. Science 365, 162–168 (2019).

    Article  Google Scholar 

  155. Liu, H. et al. Structure-based programming of lymph-node targeting in molecular vaccines. Nature 507, 519–522 (2014).

    Article  Google Scholar 

  156. Ma, L. et al. Vaccine-boosted CAR T crosstalk with host immunity to reject tumors with antigen heterogeneity. Cell 186, 3148.e20–3165.e20 (2023).

    Article  Google Scholar 

  157. Meyer, R. A. et al. Biodegradable nanoellipsoidal artificial antigen presenting cells for antigen specific T-cell activation. Small 11, 1519–1525 (2015).

    Article  Google Scholar 

  158. Kosmides, A. et al. Biomimetic biodegradable artificial antigen presenting cells synergize with PD-1 blockade to treat melanoma. Biomaterials 118, 16–26 (2017).

    Article  Google Scholar 

  159. Siegler, E. L. & Kenderian, S. S. Neurotoxicity and cytokine release syndrome after chimeric antigen receptor T cell therapy: insights into mechanisms and novel therapies. Front. Immunol. 11, 1973 (2020).

    Article  Google Scholar 

  160. Akhavan, D. et al. CAR T cells for brain tumors: lessons learned and road ahead. Immunol. Rev. 290, 60–84 (2019).

    Article  Google Scholar 

  161. Liu, Y., Sperling, A. S., Smith, E. L. & Mooney, D. J. Optimizing the manufacturing and antitumour response of CAR T therapy. Nat. Rev. Bioeng. 1, 271–285 (2023).

    Article  Google Scholar 

  162. Jafarzadeh, L., Masoumi, E., Fallah-Mehrjardi, K., Mirzaei, H. R. & Hadjati, J. Prolonged persistence of chimeric antigen receptor (CAR) T cells in adoptive cancer immunotherapy: challenges and ways forward. Front. Immunol. 11, 702 (2020).

    Article  Google Scholar 

  163. Gong, Y. et al. An injectable epigenetic autophagic modulatory hydrogel for boosting umbilical cord blood NK cell therapy prevents postsurgical relapse of triple-negative breast cancer. Adv. Sci. 9, 2201271 (2022).

    Article  Google Scholar 

  164. Kirouac, D. C. et al. Deconvolution of clinical variance in CAR-T cell pharmacology and response. Nat. Biotechnol. 41, 1655 (2023).

    Article  Google Scholar 

  165. Nash, A. M. et al. Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors. Sci. Adv. 8, eabm1032 (2022).

    Article  Google Scholar 

  166. Zmievskaya, E. et al. Application of CAR-T Cell therapy beyond oncology: autoimmune diseases and viral infections. Biomedicines 9, 59 (2021).

    Article  Google Scholar 

  167. Maldini, C. R., Ellis, G. I. & Riley, J. L. CAR T cells for infection, autoimmunity and allotransplantation. Nat. Rev. Immunol. 18, 605–616 (2018).

    Article  Google Scholar 

  168. Ferreira, L. M. R., Muller, Y. D., Bluestone, J. A. & Tang, Q. Next-generation regulatory T cell therapy. Nat. Rev. Drug. Discov. 18, 749–769 (2019).

    Article  Google Scholar 

  169. Bluestone, J. A. et al. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci. Transl. Med. 7, 315ra189 (2015).

    Article  Google Scholar 

  170. Marshall, G. P. et al. Biomaterials-based nanoparticles conjugated to regulatory T cells provide a modular system for localized delivery of pharmacotherapeutic agents. J. Biomed. Mater. Res. A 111, 185–197 (2023).

    Article  Google Scholar 

  171. van Schaik, T. A. et al. Engineered cell-based therapies in ex vivo ready-made CellDex capsules have therapeutic efficacy in solid tumors. Biomed. Pharmacother. 162, 114665 (2023).

    Article  Google Scholar 

  172. Zhang, K. et al. Evidence-based biomaterials research. Bioact. Mater. 15, 495–503 (2022).

    Google Scholar 

  173. Rosenberg, S. A., Spiess, P. & Lafreniere, R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233, 1318–1321 (1986).

    Article  Google Scholar 

  174. Naldini, L. et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272, 263–267 (1996).

    Article  Google Scholar 

  175. Majzner, R. G. & Mackall, C. L. Clinical lessons learned from the first leg of the CAR T cell journey. Nat. Med. 25, 1341–1355 (2019).

    Article  Google Scholar 

  176. Parida, S. K. et al. T-cell therapy: options for infectious diseases. Clin. Infect. Dis. 61 (Suppl. 3), S217–S224 (2015).

    Article  Google Scholar 

  177. Chaudhuri, O. Viscoelastic hydrogels for 3D cell culture. Biomater. Sci. 5, 1480–1490 (2017).

    Article  Google Scholar 

  178. Caliari, S. R. & Burdick, J. A. A practical guide to hydrogels for cell culture. Nat. Methods 13, 405–414 (2016).

    Article  Google Scholar 

  179. Prakken, B. et al. Artificial antigen-presenting cells as a tool to exploit the immune ‘synapse’. Nat. Med. 6, 1406–1410 (2000).

    Article  Google Scholar 

  180. US National Library of Medicine. ClinicalTrials.gov clinicaltrials.gov/study/NCT00850187 (2012).

  181. Valot, L., Martinez, J., Mehdi, A. & Subra, G. Chemical insights into bioinks for 3D printing. Chem. Soc. Rev. 48, 4049–4086 (2019).

    Article  Google Scholar 

  182. Monberg, T. J., Borch, T. H., Svane, I. M. & Donia, M. TIL therapy: facts and hopes. Clin. Cancer Res. 29, 3275–3283 (2023).

    Article  Google Scholar 

  183. Coukos, G. TIL therapy entering the mainstream. N. Engl. J. Med. 387, 2185–2186 (2022).

    Article  Google Scholar 

  184. Sun, Y. et al. Evolution of CD8+ T cell receptor (TCR) engineered therapies for the treatment of cancer. Cells 10, 2379 (2021).

    Article  Google Scholar 

  185. Campillo-Davo, D., Flumens, D. & Lion, E. The quest for the best: how TCR affinity, avidity, and functional avidity affect TCR-engineered T-cell antitumor responses. Cells 9, 1720 (2020).

    Article  Google Scholar 

  186. Shafer, P., Kelly, L. M. & Hoyos, V. Cancer therapy with TCR-engineered T cells: current strategies, challenges, and prospects. Front. Immunol. 13, 835762 (2022).

    Article  Google Scholar 

  187. Matsuda, T. et al. Induction of neoantigen-specific cytotoxic T cells and construction of T-cell receptor-engineered T cells for ovarian cancer. Clin. Cancer Res. 24, 5357–5367 (2018).

    Article  Google Scholar 

  188. Robbins, P. et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J. Clin. Oncol. 29, 917–924 (2011).

    Article  Google Scholar 

  189. Parkhurst, M. et al. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol. Ther. 19, 620–626 (2010).

    Article  Google Scholar 

  190. Johnson, L. A. et al. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 114, 535–546 (2009).

    Article  Google Scholar 

  191. June, C. H., O’Connor, R. S., Kawalekar, O. U., Ghassemi, S. & Milone, M. C. CAR T cell immunotherapy for human cancer. Science 359, 1361–1365 (2018).

    Article  Google Scholar 

  192. Moretti, A. et al. The past, present, and future of non-viral CAR T cells. Front. Immunol. 13, 867013 (2022).

    Article  Google Scholar 

  193. Dimitri, A., Herbst, F. & Fraietta, J. A. Engineering the next-generation of CAR T-cells with CRISPR-Cas9 gene editing. Mol. Cancer 21, 78 (2022).

    Article  Google Scholar 

  194. Khan, A. & Sarkar, E. CRISPR/Cas9 encouraged CAR-T cell immunotherapy reporting efficient and safe clinical results towards cancer. Cancer Treat. Res. Commun. 33, 100641 (2022).

    Article  Google Scholar 

  195. Tang, N. et al. TGF-β inhibition via CRISPR promotes the long-term efficacy of CAR T cells against solid tumors. JCI Insight 5, e133977 (2020).

    Article  Google Scholar 

  196. Choi, B. D. et al. CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma. J. Immunother. Cancer 7, 304 (2019).

    Article  Google Scholar 

  197. Razeghian, E. et al. A deep insight into CRISPR/Cas9 application in CAR-T cell-based tumor immunotherapies. Stem Cell Res. Ther. 12, 428 (2021).

    Article  Google Scholar 

  198. Hu, W., Wang, G., Huang, D., Sui, M. & Xu, Y. Cancer immunotherapy based on natural killer cells: current progress and new opportunities. Front. Immunol. 10, 1205 (2019).

    Article  Google Scholar 

  199. Daher, M. & Rezvani, K. Next generation natural killer cells for cancer immunotherapy: the promise of genetic engineering. Curr. Opin. Immunol. 51, 146–153 (2018).

    Article  Google Scholar 

  200. Vliet, A., Georgoudaki, A.-M., Raimo, M., de Gruijl, T. & Spanholtz, J. Adoptive NK cell therapy: a promising treatment prospect for metastatic melanoma. Cancers 13, 4722 (2021).

    Article  Google Scholar 

  201. Ishikawa, T. et al. Phase I clinical trial of adoptive transfer of expanded natural killer cells in combination with IgG1 antibody in patients with gastric or colorectal cancer. Int. J. Cancer 142, 2599–2609 (2018).

    Article  Google Scholar 

  202. Herberman, R. B., Nunn, M. E. & Lavrin, D. H. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution of reactivity and specificity. Int. J. Cancer 16, 216–229 (1975).

    Article  Google Scholar 

  203. Todorovic, Z. et al. CAR T cell therapy for chronic lymphocytic leukemia: successes and shortcomings. Curr. Oncol. 29, 3647–3657 (2022).

    Article  Google Scholar 

  204. Karagiannis, P. & Kim, S.-I. IPSC-derived natural killer cells for cancer immunotherapy. Mol. Cell 44, 541–548 (2021).

    Article  Google Scholar 

  205. Depil, S., Duchateau, P., Grupp, S., Mufti, G. & Poirot, L. ‘Off-the-shelf’ allogeneic CAR T cells: development and challenges. Nat. Rev. Drug. Discov. 19, 185–199 (2020).

    Article  Google Scholar 

  206. Goldenson, B. H., Hor, P. & Kaufman, D. S. iPSC-derived natural killer cell therapies — expansion and targeting. Front. Immunol. 13, 841107 (2022).

    Article  Google Scholar 

  207. Sloas, C., Gill, S. & Klichinsky, M. Engineered CAR-macrophages as adoptive immunotherapies for solid tumors. Front. Immunol. 12, 783305 (2021).

    Article  Google Scholar 

  208. Chung, Y. R., Dangi, T., Palacio, N., Sanchez, S. & Penaloza-MacMaster, P. Adoptive B cell therapy for chronic viral infection. Front. Immunol. 13, 908707 (2022).

    Article  Google Scholar 

  209. Jhita, N. & Raikar, S. S. Allogeneic gamma delta T cells as adoptive cellular therapy for hematologic malignancies. Explor. Immunol. 2, 334–350 (2022).

    Article  Google Scholar 

Download references

Acknowledgements

This research was partially financially supported by the Center for Human Systems Immunology with the Bill & Melinda Gates Foundation (OPP1113682; OPP1211043). A.N. was supported by the Paul and Mildred Berg Stanford Graduate Fellowship. N.E. was supported by a US National Science Foundation Graduate Research Fellowship.

Author information

Author notes

  1. These authors contributed equally: Noah Eckman, Anahita Nejatfard, Romola Cavet.

Authors and Affiliations

  1. Department of Chemical Engineering, Stanford University, Stanford, CA, USA

    Noah Eckman & Abigail K. Grosskopf

  2. Department of Biochemistry, Stanford University, Stanford, CA, USA

    Anahita Nejatfard

  3. Biological Sciences Collegiate Division, University of Chicago, Chicago, IL, USA

    Romola Cavet

  4. Department of Preclinical and Translational Pharmacokinetics and Pharmacodynamics, Genentech Inc., South San Francisco, CA, USA

    Abigail K. Grosskopf

  5. Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA

    Eric A. Appel

  6. Department of Bioengineering, Stanford University, Stanford, CA, USA

    Eric A. Appel

  7. Department of Pediatrics — Endocrinology, Stanford University, Stanford, CA, USA

    Eric A. Appel

  8. ChEM-H Institute, Stanford University, Stanford, CA, USA

    Eric A. Appel

  9. Woods Institute for the Environment, Stanford University, Stanford, CA, USA

    Eric A. Appel

Authors
  1. Noah Eckman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anahita Nejatfard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Romola Cavet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abigail K. Grosskopf
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eric A. Appel
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.K.G., R.C. and E.A.A. conceptualized the review. N.E. and A.N. wrote the paper. All authors edited and revised the paper.

Corresponding authors

Correspondence to Abigail K. Grosskopf or Eric A. Appel.

Ethics declarations

Competing interests

E.A.A. and A.K.G. are listed as inventors on a patent application (PCT/US2021/055897) that covers some of the technologies described in this manuscript. The other authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Bioengineering thanks Rui Yao, who co-reviewed with Supeng Ding, Yevgeny Brudno and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Eckman, N., Nejatfard, A., Cavet, R. et al. Biomaterials to enhance adoptive cell therapy. Nat Rev Bioeng (2024). https://doi.org/10.1038/s44222-023-00148-z

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s44222-023-00148-z

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research