Stewart, B. & Wild, C. P. World Cancer Report 2014 (World Health Organization, 2017).
Khalil, D. N., Smith, E. L., Brentjens, R. J. & Wolchok, J. D. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat. Rev. Clin. Oncol. 13, 273–290 (2016).
Postow, M. A., Callahan, M. K. & Wolchok, J. D. Immune checkpoint blockade in cancer therapy. J. Clin. Oncol. 33, 1974–1982 (2015).
Gabrilovich, D. I. & Nagaraj, S. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 9, 162–174 (2009).
Melero, I. et al. Therapeutic vaccines for cancer: an overview of clinical trials. Nat. Rev. Clin. Oncol. 11, 509–524 (2014).
Teng, F., Meng, X., Kong, L. & Yu, J. Progress and challenges of predictive biomarkers of anti PD-1/PD-L1 immunotherapy: A systematic review. Cancer lett. 414, 166–173 (2018).
Srivastava, S. & Riddell, S. R. Chimeric antigen receptor T cell therapy: challenges to bench-to-bedside efficacy. J. Immunol. 200, 459–468 (2018).
Neelapu, S. S. et al. Chimeric antigen receptor T-cell therapy—assessment and management of toxicities. Nat. Rev. Clin. Oncol. 15, 47–62 (2018).
Weber, J. S. & Mulé, J. J. Cancer immunotherapy meets biomaterials. Nat. Biotechnol. 33, 44–45 (2015).
Fan, Y. & Moon, J. J. Nanoparticle drug delivery systems designed to improve cancer vaccines and immunotherapy. Vaccines 3, 662–685 (2015).
Irvine, D. J., Hanson, M. C., Rakhra, K. & Tokatlian, T. Synthetic nanoparticles for vaccines and immunotherapy. Chem. Rev. 115, 11109–11146 (2015).
Koshy, S. T. & Mooney, D. J. Biomaterials for enhancing anti-cancer immunity. Curr. Opin. Biotechnol. 40, 1–8 (2016).
Wang, C., Ye, Y., Hochu, G. M., Sadeghifar, H. & Gu, Z. Enhanced cancer immunotherapy by microneedle patch-assisted delivery of anti-PD1 antibody. Nano Lett. 16, 2334–2340 (2016).
Chen, Q. et al. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nat. Commun. 7, 13193 (2016).
Stephan, M. T., Moon, J. J., Um, S. H., Bershteyn, A. & Irvine, D. J. Therapeutic cell engineering with surface-conjugated synthetic nanoparticles. Nat. Med. 16, 1035–1041 (2010).
Moyer, T. J., Zmolek, A. C. & Irvine, D. J. Beyond antigens and adjuvants: formulating future vaccines. J. Clin. Investig. 126, 799–808 (2016).
Milling, L., Zhang, Y. & Irvine, D. J. Delivering safer immunotherapies for cancer. Adv. Drug Deliv. Rev. 114, 79–101 (2017).
Paavonen, J. et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet 374, 301–314 (2009).
Wiemann, B. & Starnes, C. O. Coley’s toxins, tumour necrosis factor and cancer research: a historical perspective. Pharmacol. Ther. 64, 529–564 (1994).
Dranoff, G. et al. Vaccination with irradiated tumour cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting antitumour immunity. Proc. Natl Acad. Sci. USA 90, 3539–3543 (1993).
Mach, N. & Dranoff, G. Cytokine-secreting tumour cell vaccines. Curr. Opin. Immunol. 12, 571–575 (2000).
Copier, J. & Dalgleish, A. Overview of tumour cell–based vaccines. Int. Rev. Immunol. 25, 297–319 (2006).
Kantoff, P. W. et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363, 411–422 (2010).
Cheever, M. A. & Higano, C. S. PROVENGE (sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clin. Cancer Res. 17, 3520–3526 (2011).
Muraoka, D. et al. Nanogel-based immunologically stealth vaccine targets macrophages in the medulla of lymph node and induces potent antitumour immunity. ACS Nano 8, 9209–9218 (2014).
Moon, J. J. et al. Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses. Nat. Mater. 10, 243–251 (2011).
Kuai, R., Ochyl, L. J., Bahjat, K. S., Schwendeman, A. & Moon, J. J. Designer vaccine nanodiscs for personalized cancer immunotherapy. Nat. Mater. 16, 489–496 (2017).
Lynn, G. M. et al. In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that enhance vaccine immunogenicity. Nat. Biotechnol. 33, 1201–1210 (2015).
Benne, N., van Duijn, J., Kuiper, J., Jiskoot, W. & Slütter, B. Orchestrating immune responses: How size, shape and rigidity affect the immunogenicity of particulate vaccines. J. Control. Release 234, 124–134 (2016).
Walkey, C. D., Olsen, J. B., Guo, H., Emili, A. & Chan, W. C. Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. J. Am. Chem. Soc. 134, 2139–2147 (2012).
Kasturi, S. P. et al. Programming the magnitude and persistence of antibody responses with innate immunity. Nature 470, 543–547 (2011).
Mohsen, M. O. et al. Delivering adjuvants and antigens in separate nanoparticles eliminates the need of physical linkage for effective vaccination. J. Control. Release 251, 92–100 (2017).
Flach, T. L. et al. Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity. Nat. Med. 17, 479–487 (2011).
Ng, G. et al. Receptor-independent, direct membrane binding leads to cell-surface lipid sorting and syk kinase activation in dendritic cells. Immunity 29, 807–818 (2008).
Luo, M. et al. A STING-activating nanovaccine for cancer immunotherapy. Nat. Nanotech. 12, 648–654 (2017).
Oussoren, C., Zuidema, J., Crommelin, D. J. A. & Storm, G. Lymphatic uptake and biodistribution of liposomes after subcutaneous injection: II. Influence of liposomal size, lipid composition and lipid dose. Biochim. Biophys. Acta 1328, 261–272 (1997).
Reddy, S. T., Rehor, A., Schmoekel, H. G., Hubbell, J. A. & Swartz, M. A. In vivo targeting of dendritic cells in lymph nodes with poly (propylene sulfide) nanoparticles. J. Control. Release 112, 26–34 (2006).
Mueller, S. N., Tian, S. & DeSimone, J. M. Rapid and persistent delivery of antigen by lymph node targeting PRINT nanoparticle vaccine carrier to promote humoral immunity. Mol. Pharm. 12, 1356–1365 (2015).
Caminschi, I., Maraskovsky, E. & Heath, W. R. Targeting dendritic cells in vivo for cancer therapy. Front. Immunol. https://doi.org/10.3389/fimmu.2012.00013 (2012).
Rosalia, R. A. et al. CD40-targeted dendritic cell delivery of PLGA-nanoparticle vaccines induce potent antitumour responses. Biomaterials 40, 88–97 (2015).
Chen, P. et al. Dendritic cell targeted vaccines: Recent progresses and challenges. Hum. Vaccines Immunother. 12, 612–622 (2016).
Liu, H. et al. Structure-based programming of lymph-node targeting in molecular vaccines. Nature 507, 519–522 (2014).
Jabulowsky, R. A. et al. A first-in-human phase I/II clinical trial assessing novel mRNA-lipoplex nanoparticles for potent melanoma immunotherapy. Cancer Res. 77, CT034 (2017).
Study of DPX-Survivac vaccine therapy and epacadostat in patients with recurrent ovarian cancer. ClinicalTrials.gov https://clinicaltrials.gov/show/nct02785250 (2017).
Berinstein, N. L. et al. Survivin-targeted immunotherapy drives robust polyfunctional T cell generation and differentiation in advanced ovarian cancer patients. Oncoimmunology 4, e1026529 (2015).
Berinstein, N. L. et al. First-in-man application of a novel therapeutic cancer vaccine formulation with the capacity to induce multi-functional T cell responses in ovarian, breast and prostate cancer patients. J. Transl. Med. 10, 156–156 (2012).
Karkada, M., Berinstein, N. L. & Mansour, M. Therapeutic vaccines and cancer: focus on DPX-0907. Biol. Targets Ther. 8, 27–38 (2014).
Safety study of a recombinant protein vaccine to treat esophageal cancer. ClinicalTrials.gov https://clinicaltrials.gov/show/nct01003808 (2013).
Kageyama, S. et al. Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal cancer patients. J. Transl. Med. 11, 246–246 (2013).
Gribben, J. G. et al. Unexpected association between induction of immunity to the universal tumour antigen CYP1B1 and response to next therapy. Clin. Cancer Res. 11, 4430–4436 (2005).
Pitt, J. M. et al. Dendritic cell–derived exosomes for cancer therapy. J. Clin. Investig. 126, 1224–1232 (2016).
Li, Y. et al. Tumor-derived autophagosome vaccine: mechanism of cross-presentation and therapeutic efficacy. Clin. Cancer Res. 17, 7047–7057 (2011).
Combination vaccine immunotherapy (dribbles) for patients with definitively-treated stage III non-small cell lung cancer. ClinicalTrials.org https://clinicaltrials.gov/show/nct01909752 (2017).
Ali, O. A., Huebsch, N., Cao, L., Dranoff, G. & Mooney, D. J. Infection-mimicking materials to program dendritic cells in situ. Nat. Mater. 8, 151–158 (2009).
Ali, O. A., Emerich, D., Dranoff, G. & Mooney, D. J. In situ regulation of DC subsets and T cells mediates tumour regression in mice. Sci. Transl. Med. 1, 8ra19 (2009).
Ali, O. A. et al. Biomaterial-Based Vaccine Induces Regression of Established Intracranial Glioma in Rats. Pharm. Res. 28, 1074–1080 (2011).
Dendritic cell activating scaffold in melanoma. ClinicalTrials.org https://clinicaltrials.gov/show/nct01753089 (2017).
Kim, J. et al. Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy. Nat. Biotechnol. 33, 64–72 (2015).
Li, A. W. et al. A facile approach to enhance antigen response for personalized cancer vaccination. Nat. Mater. https://doi.org/10.1038/s41563-018-0028-2 (2018).
Singh, A., Suri, S. & Roy, K. In-situ crosslinking hydrogels for combinatorial delivery of chemokines and siRNA–DNA carrying microparticles to dendritic cells. Biomaterials 30, 5187–5200 (2009).
DeMuth, P. C. et al. Polymer multilayer tattooing for enhanced DNA vaccination. Nat. Mater. 12, 367–376 (2013).
Verbeke, C. S. & Mooney, D. J. Injectable, pore-forming hydrogels for in vivo enrichment of immature dendritic cells. Adv. Healthc. Mater. 4, 2677–2687 (2015).
Verbeke, C. S. et al. Multicomponent injectable hydrogels for antigen-specific tolerogenic immune modulation. Adv. Healthc. Mater. 6, 1600773 (2017).
Bencherif, S. A. et al. Injectable cryogel-based whole-cell cancer vaccines. Nat. Commun. 6, 7556 (2015).
Sexton, A. et al. A protective vaccine delivery system for in vivo T cell stimulation using nanoengineered polymer hydrogel capsules. ACS Nano 3, 3391–3400 (2009).
Umeki, Y. et al. Induction of potent antitumour immunity by sustained release of cationic antigen from a DNA‐based hydrogel with adjuvant activity. Adv. Funct. Mater. 25, 5758–5767 (2015).
Nishikawa, M. et al. Injectable, self-gelling, biodegradable, and immunomodulatory DNA hydrogel for antigen delivery. J. Control. Release 180, 25–32 (2014).
Park, C. G. et al. Extended release of perioperative immunotherapy prevents tumour recurrence and eliminates metastases. Sci. Transl. Med. 10, eaar1916 (2018).
Kim, Y.-C., Park, J.-H. & Prausnitz, M. R. Microneedles for drug and vaccine delivery. Adv. Drug Deliv. Rev. 64, 1547–1568 (2012).
DeMuth, P. C. et al. Polymer multilayer tattooing for enhanced DNA vaccination. Nat. Mater. 12, 367–376 (2013).
Eggermont, L. J., Paulis, L. E., Tel, J. & Figdor, C. G. Towards efficient cancer immunotherapy: advances in developing artificial antigen-presenting cells. Trends Biotechnol. 32, 456–465 (2014).
Zheng, Y. et al. In vivo targeting of adoptively transferred T-cells with antibody- and cytokine-conjugated liposomes. J. Control. Release 172, 426–435 (2013).
Francis, D. M. & Thomas, S. N. Progress and opportunities for enhancing the delivery and efficacy of checkpoint inhibitors for cancer immunotherapy. Adv. Drug Deliv. Rev. 15, 33–42 (2017).
Meir, R. et al. Fast image-guided stratification using anti-programmed death ligand 1 gold nanoparticles for cancer immunotherapy. ACS Nano 11, 11127–11134 (2017).
Sunshine, J. C., Perica, K., Schneck, J. P. & Green, J. J. Particle shape dependence of CD8+ T cell activation by artificial antigen presenting cells. Biomaterials 35, 269–277 (2014).
Steenblock, E. R. & Fahmy, T. M. A comprehensive platform for ex vivo T-cell expansion based on biodegradable polymeric artificial antigen-presenting cells. Mol. Ther. 16, 765–772 (2008).
Prakken, B. et al. Artificial antigen-presenting cells as a tool to exploit the immune ‘synapse’. Nat. Med. 6, 1406–1410 (2000).
Perica, K. et al. Magnetic field-induced T cell receptor clustering by nanoparticles enhances T cell activation and stimulates antitumour activity. ACS Nano 8, 2252–2260 (2014).
Fadel, T. R. et al. A carbon nanotube–polymer composite for T-cell therapy. Nat. Nanotech. 9, 639–647 (2014).
Rasmussen, A.-M. et al. Ex vivo expansion protocol for human tumour specific T cells for adoptive T cell therapy. J. Immunol. Methods 355, 52–60 (2010).
Gijs, M. A. M., Lacharme, F. & Lehmann, U. Microfluidic applications of magnetic particles for biological analysis and catalysis. Chem. Rev. 110, 1518–1563 (2010).
Laux, I. et al. Response differences between human CD4+ and CD8+ T-cells during CD28 co-stimulation: implications for immune cell-based therapies and studies related to the expansion of double-positive T-cells during aging. Clin. Immunol. 96, 187–197 (2000).
Zhang, H. et al. 4–1BB is superior to CD28 co-stimulation for generating CD8(+) cytotoxic lymphocytes for adoptive immunotherapy. J. Immunol. 179, 4910–4918 (2007).
Cheung, A. S., Zhang, D. K. Y., 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).
Ugel, S. et al. In vivo administration of artificial antigen presenting cells activates low avidity T cells for treatment of cancer. Cancer Res. 69, 9376–9384 (2009).
Shen, C., Zhang, J., Xia, L., Meng, F. & Xie, W. Induction of tumour antigen-specific cytotoxic T cell responses in naïve mice by latex microspheres-based artificial antigen-presenting cell constructs. Cell. Immunol. 247, 28–35 (2007).
Stephan, S. B. et al. Biopolymer implants enhance the efficacy of adoptive T-cell therapy. Nat. Biotechnol. 33, 97–101 (2014).
Thelin, M. A. et al. In vivo enrichment of diabetogenic T cells. Diabetes 66, 2220–2229 (2017).
Rahimian, S. et al. Polymeric microparticles for sustained and local delivery of antiCD40 and antiCTLA-4 in immunotherapy of cancer. Biomaterials 61, 33–40 (2015).
Li, Y. et al. Hydrogel dual delivered celecoxib and anti-PD-1 synergistically improve antitumour immunity. OncoImmunology 5, e1074374 (2016).
Wang, C. et al. In situ formed reactive oxygen species–responsive scaffold with gemcitabine and checkpoint inhibitor for combination therapy. Sci. Transl. Med. 10, eaan3682 (2018).
Wang, C. et al. In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy. Nat. Biomed. Eng. 1, 0011 (2017).
Ishihara, J. et al. Matrix-binding checkpoint immunotherapies enhance antitumour efficacy and reduce adverse events. Sci. Transl. Med. 9, eaan0401 (2017).
Wang, C. et al. Immunological responses triggered by photothermal therapy with carbon nanotubes in combination with anti-CTLA-4 therapy to inhibit cancer metastasis. Adv. Mater. 26, 8154–8162 (2014).
Duan, X. et al. Photodynamic therapy mediated by nontoxic core–shell nanoparticles synergizes with immune checkpoint blockade to elicit antitumour immunity and antimetastatic effect on breast cancer. J. Am. Chem. Soc 138, 16686–16695 (2016).
Min, Y. et al. Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy. Nat. Nanotech. 12, 877–882 (2017).
He, C. et al. Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy. Nat. Commun. 7, 12499 (2016).
Tumeh, P. C. et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515, 568–571 (2014).
Ali, O. A., Lewin, S. A., Dranoff, G. & Mooney, D. J. Vaccines combined with immune checkpoint antibodies promote cytotoxic T-cell activity and tumour eradication. Cancer Immunol. Res. 4, 95–100 (2016).
DPX-Survivac and checkpoint inhibitor in DLBCL. ClinicalTrials.org https://clinicaltrials.gov/show/nct03349450 (2018).
Shimizu, T. et al. Nanogel DDS enables sustained release of IL-12 for tumour immunotherapy. Biochem. Biophys. Res. Commun. 367, 330–335 (2008).
Dow, S. W. et al. Intravenous cytokine gene delivery by lipid-DNA complexes controls the growth of established lung metastases. Hum. Gene Ther. 10, 2961–2972 (1999).
Park, J. et al. Combination delivery of TGF-β inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy. Nat. Mater. 11, 895–905 (2012).
Schmid, A. S., Tintor, D. & Neri, D. Novel antibody-cytokine fusion proteins featuring granulocyte-colony stimulating factor, interleukin-3 and interleukin-4 as payloads. J. Biotechnol. 271, 29–36 (2018).
Rekers, N. H. et al. The immunocytokine L19-IL2: An interplay between radiotherapy and long-lasting systemic antitumour immune responses. OncoImmunology 7, 1414119 (2018).
Charych, D. H. et al. NKTR-214, an engineered cytokine with biased IL2 receptor binding, increased tumour exposure, and marked efficacy in mouse tumour models. Clin. Cancer Res. 22, 680–690 (2016).
Noy, R. & Pollard Jeffrey W. Tumor-associated macrophages: from mechanisms to therapy. Immunity 41, 49–61 (2014).
Zhang, Q.-w et al. Prognostic significance of tumour-associated macrophages in solid tumour: a meta-analysis of the literature. PLOS One 7, e50946 (2012).
Sica, A. & Mantovani, A. Macrophage plasticity and polarization: in vivo veritas. The J. Clin. Investig. 122, 787–795 (2012).
Ngambenjawong, C., Gustafson, H. H. & Pun, S. H. Progress in tumour-associated macrophage (TAM)-targeted therapeutics. Adv. Drug Deliv. Rev. 114, 206–221 (2017).
Zeisberger, S. M. et al. Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach. Br. J. Cancer 95, 272–281 (2006).
Shen, S. et al. Spatial targeting of tumour-associated macrophages and tumour cells with a pH-sensitive cluster nanocarrier for cancer chemoimmunotherapy. Nano Lett. 17, 3822–3829 (2017).
Ernsting, M. J. et al. Targeting of metastasis-promoting tumour-associated fibroblasts and modulation of pancreatic tumour-associated stroma with a carboxymethylcellulose-docetaxel nanoparticle. J. Control. Release 206, 122–130 (2015).
Pucci, F. et al. SCS macrophages suppress melanoma by restricting tumour-derived vesicle–B cell interactions. Science 352, 242–246 (2016).
Ohnishi, K. et al. CD169-positive macrophages in regional lymph nodes are associated with a favorable prognosis in patients with colorectal carcinoma. Cancer Sci. 104, 1237–1244 (2013).
Shiota, T. et al. The clinical significance of CD169-positive lymph node macrophage in patients with breast cancer. PLOS One 11, e0166680 (2016).
Wang, Y. et al. Polymeric nanoparticles promote macrophage reversal from M2 to M1 phenotypes in the tumour microenvironment. Biomaterials 112, 153–163 (2017).
Huang, Z. et al. Targeted delivery of oligonucleotides into tumour-associated macrophages for cancer immunotherapy. J. Control. Release 158, 286–292 (2012).
Zanganeh, S. et al. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat. Nanotech. 11, 986–994 (2016).
Song, M., Liu, T., Shi, C., Zhang, X. & Chen, X. Bioconjugated manganese dioxide nanoparticles enhance chemotherapy response by priming tumour-associated macrophages toward M1-like phenotype and attenuating tumour hypoxia. ACS Nano 10, 633–647 (2016).
Shvedova, A. A. et al. Carbon nanotubes enhance metastatic growth of lung carcinoma via up‐regulation of myeloid‐derived suppressor cells. Small 9, 1691–1695 (2013).
Wesolowski, R., Markowitz, J. & Carson, W. E. Myeloid derived suppressor cells – a new therapeutic target in the treatment of cancer. J. Immunother. Cancer https://doi.org/10.1186/2051-1426-1-10 (2013).
Kourtis, I. C. et al. Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumours in mice. PLOS One 8, e61646 (2013).
Jeanbart, L., Kourtis, I. C., van der Vlies, A. J., Swartz, M. A. & Hubbell, J. A. 6-thioguanine-loaded polymeric micelles deplete myeloid-derived suppressor cells and enhance the efficacy of T cell immunotherapy in tumour-bearing mice. Cancer Immunol. Immunother. 64, 1033–1046 (2015).
Sasso, M. S. et al. Low dose gemcitabine-loaded lipid nanocapsules target monocytic myeloid-derived suppressor cells and potentiate cancer immunotherapy. Biomaterials 96, 47–62 (2016).
Topalian, S. L., Taube, J. M., Anders, R. A. & Pardoll, D. M. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat. Rev. Cancer 16, 275–287 (2016).
Sharma, P. & Allison, J. P. The future of immune checkpoint therapy. Science 348, 56–61 (2015).
Freiburghaus, C. et al. Synergistic effects of agonistic co-stimulatory antibodies adsorbed to amphiphilic poly (γ-glutamic acid) nanoparticles. J. Immunother. Cancer 1, P128 (2013).
Mi, Y. et al. A dual immunotherapy nanoparticle improves T‐cell activation and cancer immunotherapy. Adv. Mater. 30, 1706098 (2018).
Schumacher, T. N. & Schreiber, R. D. Neoantigens in cancer immunotherapy. Science 348, 69–74 (2015).