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Adoptive cell transfer: a clinical path to effective cancer immunotherapy

Key Points

  • Adoptive cell therapy (ACT) is a treatment that uses a cancer patient's own T lymphocytes with anti-tumour activity, expanded in vitro and reinfused into the patient with cancer.

  • ACT using autologous tumour-infiltrating lymphocytes is currently the most effective treatment for patients with metastatic melanoma and can mediate objective tumour regressions in 50% of patients.

  • Lymphodepletion before ACT is an important component of the treatment because it eliminates T regulatory cells and eliminates lymphocytes, which compete with the transferred cells for homeostatic cytokines such as interleukin 7 (IL7) and IL15.

  • ACT can be effective in treating selected patients with post-transplant lymphoproliferative diseases (PTLD) resulting from Epstein–Barr virus, which can cause PTLD during the immunosuppressed state.

  • Recent studies have shown that genetic modification of lymphocytes using retroviruses that encode T-cell receptors can convert normal lymphocytes into lymphocytes with anti-cancer activity. The adoptive transfer of these lymphocytes into patients with metastatic melanoma can mediate tumour regression.

Abstract

Adoptive cell therapy (ACT) using autologous tumour-infiltrating lymphocytes has emerged as the most effective treatment for patients with metastatic melanoma and can mediate objective cancer regression in approximately 50% of patients. The use of donor lymphocytes for ACT is an effective treatment for immunosuppressed patients who develop post-transplant lymphomas. The ability to genetically engineer human lymphocytes and use them to mediate cancer regression in patients, which has recently been demonstrated, has opened possibilities for the extension of ACT immunotherapy to patients with a wide variety of cancer types and is a promising new approach to cancer treatment.

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Figure 1: The generation of anti-tumour T cells used for adoptive cell therapy.
Figure 2: Examples of objective tumour regressions in patients receiving adoptive cell transfer of autologous anti-tumour lymphocytes following a lymphodepleting preparative regimen.
Figure 3: The steps involved in generating anti-tumour T cells by inserting genes encoding T-cell receptors.
Figure 4: Diagram of the retroviral constructs used to insert T-cell receptor (TCR) genes in T cells.

References

  1. 1

    Rosenberg, S. A. et al. Use of tumor infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. Preliminary report. N. Engl. J. Med. 319, 1676–1680 (1988). The first paper to demonstrate the regression of cancer using TIL for the immunotherapy of patients with metastatic melanoma.

    CAS  Article  Google Scholar 

  2. 2

    Dudley, M. E. et al. Cancer regression and autoimmunity in patients following clonal repopulation with anti-tumor lymphocytes. Science 298, 850–854 (2002).

    CAS  Article  Google Scholar 

  3. 3

    Dudley, M. E. et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J. Clin. Oncol. 23, 2346–2357 (2005). References 2 and 3 demonstrate that lymphodepletion prior to ACT can lead to increased cancer regression as well as clonal repopulation of patients with anti-tumour lymphocytes.

    CAS  Article  Google Scholar 

  4. 4

    Morgan, R. A. et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314, 126–129 (2006). The first paper demonstrating the adoptive cell transfer of lymphocytes transduced with a retrovirus encoding TCRs that recognize a cancer antigen can mediate anti-tumour responses in patients with metastatic melanoma.

    CAS  Article  Google Scholar 

  5. 5

    Rosenberg, S. A. et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N. Engl. J. Med. 313, 1485–1492 (1985).

    CAS  Article  Google Scholar 

  6. 6

    Rosenberg, S. A., Yang, J. C., White, D. E. & Steinberg, S. M. Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2. Ann. Surg. 228, 307–319 (1998).

    CAS  Article  Google Scholar 

  7. 7

    Lotze, M. T. et al. High dose recombinant interleukin-2 in the treatment of patients with disseminated cancer: responses, treatment related morbidity and histologic findings. J. Am. Med. Assoc. 256, 3117–3124 (1986).

    CAS  Article  Google Scholar 

  8. 8

    Kammula, U. S., White, D. E. & Rosenberg, S. A. Trends in the safety high dose bolus interleukin-2 administration in patients with metastatic cancer. Cancer 83, 797–805 (1998).

    CAS  Article  Google Scholar 

  9. 9

    Phan, G. Q. et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc. Natl Acad. Sci. USA 100, 8372–8377 (2003).

    CAS  Article  Google Scholar 

  10. 10

    Attia, P. et al. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J. Clin. Oncol. 23, 6043–6053 (2005).

    CAS  Article  Google Scholar 

  11. 11

    Van der Bruggen, P. et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254, 1643–1647 (1991).

    CAS  Article  Google Scholar 

  12. 12

    Rosenberg, S. A. A new era for cancer immunotherapy based on the genes that encode cancer antigens. Immunity 10, 281–287 (1999).

    CAS  Article  Google Scholar 

  13. 13

    Rosenberg, S. A., Yang, J. C. & Restifo, N. P. Cancer immunotherapy: moving beyond current vaccines. Nature Med. 10, 909–915 (2004).

    CAS  Article  Google Scholar 

  14. 14

    Rosenberg, S. A. et al. Tumor progression can occur despite the induction of very high levels of self/tumor antigen-specific CD8+ T cells in patients with melanoma. J. Immunol. 175, 6169–6176 (2005). The demonstration that peptide vaccines are capable of generating large numbers of anti-tumour lymphocytes in vivo , but these lymphocytes do not appear to have any in vivo ability to prevent recurrence.

    CAS  Article  Google Scholar 

  15. 15

    Mitchison, N. A. Studies on the immunological response to foreign tumor transplants in the mouse. I. The role of lymph node cells in conferring immunity by adoptive transfer. J. Exp. Med. 102, 157–177 (1955). A seminal paper demonstrating the role of the cellular immune response in the rejection of tumour transplants.

    CAS  Article  Google Scholar 

  16. 16

    Delorme, E. J. & Alexander, P. Treatment of primary fibrosarcoma in the rat with immune lymphocytes. Lancet 2, 117–120 (1964).

    CAS  Article  Google Scholar 

  17. 17

    Fefer, A. Immunotherapy and chemotherapy of Moloney sarcoma virus-induced tumors in mice. Cancer Res. 29, 2177–2183 (1969).

    CAS  PubMed  Google Scholar 

  18. 18

    Cheever, M. A., Kempf, R. A. & Fefer, A. Tumor neutralization, immunotherapy, and chemoimmunotherapy of a Friend leukemia with cells secondarily sensitized in vitro. J. Immunol. 119, 714–718 (1977).

    CAS  PubMed  Google Scholar 

  19. 19

    Eberlein, T. J., Rosenstein, M. & Rosenberg, S. A. Regression of a disseminated syngeneic solid tumor by systemic transfer of lymphoid cells expanded in IL-2. J. Exp. Med. 156, 385–397 (1982). Demonstration that the intravenous administration of anti-tumour lymphocytes expanded in IL2 could mediate the regression of established disseminated syngeneic tumours in mice.

    CAS  Article  Google Scholar 

  20. 20

    Donohue, J. H. et al. The systemic administration of purified interleukin-2 enhances the ability of sensitized murine lymphocyte to cure a disseminated syngeneic lymphoma. J. Immunol. 132, 2123–2128 (1984).

    CAS  PubMed  Google Scholar 

  21. 21

    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). The first demonstration in murine models that the adoptive transfer of TIL could mediate the regression of established murine tumours.

    CAS  Article  Google Scholar 

  22. 22

    Overwijk, W. W. et al. Tumor regression and autoimmunity after reversal of a functionally tolerant state of self-reactive CD8+ T cells. J. Exp. Med. 198, 569–580 (2003). This paper demonstrated that adoptive cell transfer, vaccine and IL2 administration could mediate the rejection of large established transgenic B16 melanomas in mice.

    CAS  Article  Google Scholar 

  23. 23

    Antony, P. A. et al. CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. J. Immunol. 174, 2591–2601 (2005).

    CAS  Article  Google Scholar 

  24. 24

    Gattinoni, L. et al. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J. Exp. Med. 202, 907–912 (2005).

    CAS  Article  Google Scholar 

  25. 25

    Wrzesiniski, C. et al. Hematopoietic stem cells promote the expansion and function of adoptively transferred antitumor CD8 T cells. J. Clin. Invest. 117, 492–501 (2007).

    Article  Google Scholar 

  26. 26

    Gattinoni, L. et al. Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells. J. Clin. Invest. 115, 1616–1626 (2005).

    CAS  Article  Google Scholar 

  27. 27

    Paulos, C. M. et al. Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling. J. Clin. Invest. 117, 2197–2204 (2007).

    CAS  Article  Google Scholar 

  28. 28

    Abad, J. D. et al. T-cell receptor gene therapy of established tumors in a murine melanoma model. J. Immunother. 31, 1–6 (2008).

    CAS  Article  Google Scholar 

  29. 29

    Muul, L. M., Spiess, P. J., Director, E. P. & Rosenberg, S. A. Identification of specific cytolytic immune responses against autologous tumor in humans bearing malignant melanoma. J. Immunol. 138, 989–995 (1987). The first description of the ability of TIL in the human to recognize human tumour antigens presented on cancer cells.

    CAS  PubMed  Google Scholar 

  30. 30

    Dudley, M. E., Wunderlich, J. R., Shelton, T. E., Even, J. & Rosenberg, S. A. Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. J. Immunother. 26, 332–342 (2003).

    Article  Google Scholar 

  31. 31

    Rosenberg, S. A. et al. Treatment of patients with metastatic melanoma using autologous tumor-infiltrating lymphocytes and interleukin-2. J. Natl Cancer Inst. 86, 1159–1166 (1994).

    CAS  Article  Google Scholar 

  32. 32

    Aebersold, P. et al. Lysis of autologous melanoma cells by tumor infiltrating lymphocytes: association with clinical response. J. Natl Cancer Inst. 13, 932–937 (1991).

    Article  Google Scholar 

  33. 33

    Schwartzentruber, D. J. et al. In vitro predictors of therapeutic response in melanoma patients receiving tumor infiltrating lymphocytes and interleukin-2. J. Clin. Oncol. 12, 1475–1483 (1994).

    CAS  Article  Google Scholar 

  34. 34

    Rosenberg, S. A. et al. Gene transfer into humans: immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N. Engl. J. Med. 323, 570–578 (1990).

    CAS  Article  Google Scholar 

  35. 35

    Dummer, W. et al. T cell homeostatic proliferation elicits effective antitumor autoimmunity. J. Clin. Invest. 110, 185–192 (2002).

    CAS  Article  Google Scholar 

  36. 36

    Yee, C. et al. Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc. Natl Acad. Sci. USA 99, 16168–16173 (2002).

    CAS  Article  Google Scholar 

  37. 37

    Robbins, P. F. et al. Cutting edge: persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy. J. Immunol. 173, 7125–7130 (2004). This paper demonstrated that persistence of adoptively transferred cells correlated directly with the likelihood of cancer regression.

    CAS  Article  Google Scholar 

  38. 38

    Zhou, J., Shen, X., Hodes, R. J., Rosenberg, S. A. & Robbins, P. Telomere length of transferred lymphocytes correlates with in vivo persistence and tumor regression in melanoma patients receiving cell transfer therapy. J. Immunol. 175, 7046–7052 (2005). The paper shows that the telomere length of the transferred lymphocytes correlated both with in vivo persistence of the transferred cells as well as with tumour regression.

    CAS  Article  Google Scholar 

  39. 39

    Powell, D. J., Dudley, M. E., Robbins, P. F. & Rosenberg, S. A. Transition of late-stage effector T cells to CD27+ CD28+ tumor-reactive effector memory T cells in humans after adoptive cell transfer therapy. Blood 101, 241–250 (2004).

    Google Scholar 

  40. 40

    Ochsenbein, A. F. et al. CD27 expression promotes long-term survival of functional effector-memory CD8+ cytotoxic T lymphocytes in HIV-infected patients. J. Exp. Med. 200, 1407–1417 (2004).

    CAS  Article  Google Scholar 

  41. 41

    Marijt, W. A. E. et al. Hematopoiesis-restricted minor histocompatibility antigens HA-1 or HA-2-specific T cells can induce complete remissions of relapsed leukemia. Proc. Natl Acad. Sci. USA 100, 2742–2747 (2003).

    CAS  Article  Google Scholar 

  42. 42

    Kolb, H. J. et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 76, 2462–2465 (1990). This paper was the first to show that treatment with donor lymphocytes could mediate cytogenetic remissions in patients with chronic myeloid leukaemia.

    CAS  PubMed  Google Scholar 

  43. 43

    Mackinnon, S. et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease. Blood 86, 1261–1268 (1995).

    CAS  PubMed  Google Scholar 

  44. 44

    Riddell, S. R., Bleakley, M., Nishida, T., Berger, C. & Warren, E. H. Adoptive transfer of allogeneic antigen-specific T cells. Biol. Blood Marrow Transplant. 12, 9–12 (2006).

    CAS  Article  Google Scholar 

  45. 45

    Papadopoulos, E. B. et al. Infusions of donor leukocytes to treat Epstein–Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation. N. Engl. J. Med. 330, 1185–1191 (1994). This paper showed that the infusion of normal donor lymphocytes could achieve complete responses in patients with lymphomas that occurred following the treatment of leukaemia with chemotherapy and T-cell-depleted allogeneic stem cell grafts.

    CAS  Article  Google Scholar 

  46. 46

    Rooney, C. M. et al. Use of gene-modified virus-specific T lymphocytes to control Epstein–Barr-virus-related lymphoproliferation. Lancet 345, 9–13 (1995).

    CAS  Article  Google Scholar 

  47. 47

    Rooney, C. M. et al. Infusion of cytotoxic T cells for the prevention and treatment of Epstein–Barr virus-induced lymphoma in allogeneic transplant recipients. Blood 92, 1549–1555 (1998). References 46 and 47 showed that tumour regression could be obtained by the infusion of long-term cultured EBV-specific T-cell lines.

    CAS  PubMed  Google Scholar 

  48. 48

    Khanna, R. et al. Activation and adoptive transfer of Epstein–Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease. Proc. Natl Acad. Sci. USA 96, 10391–10396 (1999).

    CAS  Article  Google Scholar 

  49. 49

    Haque, T. et al. Complete regression of posttransplant lymphoproliferative disease using partially HLA-matched Epstein–Barr virus-specific cytotoxic T cells. Transplantation 72, 1399–1402 (2001).

    CAS  Article  Google Scholar 

  50. 50

    Haque, T. et al. Allogeneic cytotoxic T cell therapy for EBV-positive post transplant lymphoproliferative disease: results of a phase 2 multicentre clinical trial. Blood 110, 1123–1131 (2007).

    CAS  Article  Google Scholar 

  51. 51

    Straathof, K. et al. Treatment of nasopharyngeal carcinoma with Epstein–Barr virus-specific T lymphocytes. Blood 105, 1898–1904 (2005).

    CAS  Article  Google Scholar 

  52. 52

    Comoli, P. et al. Cell therapy of stage IV nasopharyngeal carcinoma with autologous Epstein–Barr virus-targeted cytotoxic T lymphocytes. J. Clin. Oncol. 23, 8942–8949 (2005).

    CAS  Article  Google Scholar 

  53. 53

    Bollard, C. et al. Cytotoxic T lymphocyte therapy for Epstein–Barr virus Hodgkin's disease. J. Exp. Med. 200, 1623–1633 (2004).

    CAS  Article  Google Scholar 

  54. 54

    Riddell, S. R. et al. Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science 257, 238–241 (1992).

    CAS  Article  Google Scholar 

  55. 55

    Sadelain, M., Riviere, I. & Brentjens, R. Targeting tumours with genetically enhanced T lymphocytes. Nature Rev. Cancer 3, 35–45 (2003).

    CAS  Article  Google Scholar 

  56. 56

    Murphy, A. et al. Gene modification strategies to induce tumor immunity. Immunity 22, 403–414 (2005).

    CAS  Article  Google Scholar 

  57. 57

    Cole, D. J. et al. Characterization of the functional specificity of a cloned T-cell receptor heterodimer recognizing the MART-1 melanoma antigen. Cancer Res. 55, 748–752 (1995).

    CAS  PubMed  Google Scholar 

  58. 58

    Hughes, M. S. et al. Transfer of a TCR gene derived from a patient with a marked antitumor response conveys highly active T-cell effector functions. Hum. Gene. Ther. 16, 457–472 (2005).

    CAS  Article  Google Scholar 

  59. 59

    Morgan, R. A. et al. High efficiency TCR gene transfer into primary human lymphocytes affords avid recognition of melanoma tumor antigen glycoprotein 100 and does not alter the recognition of autologous melanoma antigens. J. Immunol. 171, 3287–3295 (2003).

    CAS  Article  Google Scholar 

  60. 60

    Zhao, Y. et al. Primary human lymphocytes transduced with NY-ESO-1 antigen-specific TCR genes recognize and kill diverse human tumor cell lines. J. Immunol. 174, 4415–4423 (2005).

    CAS  Article  Google Scholar 

  61. 61

    Cohen, C. J., Zhao, Y., Zheng, Z., Rosenberg, S. A. & Morgan, R. A. Enhanced antitumor activity of murine-human hybrid T-cell receptor (TCR) in human lymphocytes is associated with improved pairing and TCR/CD3 stability. Cancer Res. 66, 8878–8886 (2006).

    CAS  Article  Google Scholar 

  62. 62

    Cohen, C. J. et al. Enhanced antitumor activity of T cells engineered to express T-cell receptors with a second disulfide bond. Cancer Res. 67, 3898–3903 (2007).

    CAS  Article  Google Scholar 

  63. 63

    Theobald, M. B. J., Dittmer, D., Levine, A. J. & Sherman, L. A. Targeting p53 as a general tumor antigen. Proc. Natl Acad. Sci. USA 92, 11993–11997 (1995).

    CAS  Article  Google Scholar 

  64. 64

    Kuball, J., Schmitz, F. W. & Voss, R. H. Cooperation of human tumor-reactive CD4+ and CD8+ T cells after redirection of their specificity by a high-affinity p53A2.1-specific TCR. Immunity 22, 117–129 (2005).

    CAS  Article  Google Scholar 

  65. 65

    Cohen, C. J. et al. Recognition of fresh human tumor by human peripheral blood lymphocytes transduced with a bicistronic retroviral vector encoding a murine anti-p53 TCR. J. Immunol. 175, 5799–5808 (2005). References 58–65 demonstrate that TCRs can be identified that recognize cancer antigens and that transduction of these TCRs into normal human cells can transfer this antigen recognition.

    CAS  Article  Google Scholar 

  66. 66

    Li, Y. et al. Directed evolution of human T-cell receptors with picomolar affinities by phage display. Nature Biotech. 23, 349–354 (2005).

    CAS  Article  Google Scholar 

  67. 67

    Gross, G., Waks, T. & Eshhar, Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc. Natl Acad. Sci. USA 86, 10024–10028 (1989).

    CAS  Article  Google Scholar 

  68. 68

    Kershaw, M. H. et al. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin. Cancer Res. 12, 6106–6115 (2006).

    CAS  Article  Google Scholar 

  69. 69

    Lamers, C. H. J. et al. Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J. Clin. Oncol. 24, e20–e22 (2006).

    Article  Google Scholar 

  70. 70

    Park, J. R. et al. Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Mol. Ther. 15, 825–833 (2007).

    CAS  Article  Google Scholar 

  71. 71

    Brentjens R. J. et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. Nature Med. 9, 279–286 (2003).

    CAS  Article  Google Scholar 

  72. 72

    Johnson, L. A. et al. Gene transfer of tumor-reactive TCR confers both high avidity and tumor reactivity to nonreactive peripheral blood mononuclear cells and tumor-infiltrating. J. Immunol. 177, 6548–6559 (2006).

    CAS  Article  Google Scholar 

  73. 73

    Fernandez-Cruz, E., Woda, B. A. & Feldman, J. D. Elimination of syngeneic sarcomas in rats by a subset of T lymphocytes. J. Exp. Med. 152, 823–841 (1980).

    CAS  Article  Google Scholar 

  74. 74

    Berendt, M. J. & North, R. J. T-cell-mediated suppression of anti-tumor immunity: an explanation for progressive growth of an immunogenic tumor. J. Exp. Med. 151, 69–80 (1980).

    CAS  Article  Google Scholar 

  75. 75

    Mule, J. J., Shu, S., Schwarz, S. L. & Rosenberg, S. A. Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2. Science 225, 1487–1489 (1984).

    CAS  Article  Google Scholar 

  76. 76

    Liu, K. & Rosenberg, S. A. Transduction of an interleukin-2 gene into human melanoma-reactive lymphocytes results in their continued growth in the absence of exogenous IL-2 and maintenance of specific antitumor activity. J. Immunol. 167, 6356–6365 (2001).

    CAS  Article  Google Scholar 

  77. 77

    Waldmann, T. A. The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nature Rev. Immunol. 6, 595–601 (2007).

    Article  Google Scholar 

  78. 78

    Ruggeri, L., Mancusi, A., Capanni, M., Martelli, M. F. & Velardi, A. Exploitation of alloreactive NK cells in adoptive immunotherapy of cancer. Curr. Opin. Immunol. 17, 211–217 (2005).

    CAS  Article  Google Scholar 

  79. 79

    Dudley, M. E. et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J. Clin. Oncol. (in the press).

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Correspondence to Steven A. Rosenberg.

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DATABASES

National Cancer Institute

chronic myeloid leukaemia

melanoma

multiple myeloma

nasopharyngeal cancer

renal cancer

National Cancer Institute Drug Dictionary

cyclophosphamide

fludarabine

Glossary

Adoptive cell therapy

(ACT). The administration of a patient's own (autologous) or donor (allogeneic) anti-tumour lymphocytes following a lymphodepleting preparative regimen.

Capillary leak syndrome

The loss of intravascular fluid into soft tissues and lung.

Objective clinical response

The Response Evaluation Criteria in Solid Tumours (RECIST) defines an objective response as a 30% reduction in the sum of the longest diameters of measurable lesions comparing post-treatment with pretreatment values. The World Health Organization criterion defines an objective response to be a 50% reduction in the sum of the products of perpendicular diameters of measurable lesions. In both criteria no new lesions can appear.

Avidity

The relative intensity of reactivity of lymphocytes when interacting with antigen.

Allogeneic

Inter-individual genetic variation at the MHC locus. In a partially matched transplant, for example, some MHC antigens are shared by donor and recipient, but in addition the donor has some MHC antigens that the recipient does not.

Lymphodepletion

Lymphodepletion before ACT uses total body irradiation or cytotoxic drugs to deplete the lymphoid compartment of patients.

Central memory cells

A subset of antigen-reactive lymphocytes with markers such as CD62L and CCR7 that indicate a less differentiated phenotype.

Antigen-presenting cells

(APC). A subset of cells that have characteristics enabling them to efficiently present antigenic epitopes to lymphocytes (for example, dendritic cells).

Non-myeloablative

Relatively modest to moderate doses of chemotherapy are given, not to attack the cancer, but just to suppress the immune system for a brief period of a week or so.

Effector phenotype

A constellation of cell surface markers that indicate that lymphocytes have differentiated into a mature effector cell capable of recognizing antigen and lysing target cells or secreting cytokines when encountering antigen.

Alloantigens

An antigen that exists in alternative (allelic) forms in a species, thus inducing an immune response when one form is transferred to members of the species who lack it.

Buffy coat cells

The plasma layer containing enriched white blood cells that results when whole blood is centrifuged.

Chronic phase

Indolent phase of the disease in patients with chronic myeloid leukaemia.

Blast crisis

Aggressive acute phase of the disease in patients with chronic myeloid leukaemia.

Graft-versus-host disease

Inflammatory and tissue-destructive immune reactions that result from the attack on host tissues by infused allogeneic lymphocytes.

Post-transplant lymphoproliferative disease

(PTLD). Neoplastic proliferation of lymphocytes that occurs in patients undergoing immunosuppresion, often in preparation for bone marrow or organ transplantation; can occur in host or recipient cells.

Reed–Sternberg cells

Cells with a characteristic morphology that are thought to be the malignant cells in patients with Hodgkin lymphoma.

Tolerance

The process that ensures that B- and T-cell repertoires are biased against self-reactivity, reducing the likelihood of autoimmunity.

Carcinoembryonic antigen

A protein found in fetal gastrointestinal tissue that can be upregulated in some gastrointestinal cancers and can serve as a marker of tumour burden.

Cancer–testis antigen

A class of antigenic proteins present on some human cancers but not on adult normal tissues except for testes.

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Rosenberg, S., Restifo, N., Yang, J. et al. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 8, 299–308 (2008). https://doi.org/10.1038/nrc2355

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