Tumor immunotherapy in melanoma: On the dawn of a new era?

Current Opinion in Molecular Therapeutics

Volumn 9, Issue 1, 2007, Pages 70-78

  Wilcox, Ryan ^a   Markovic, Svetomir N ^a  

^a MAYO CLINIC COLLEGE OF MEDICINE   (United States)

Author keywords

Adoptive immunotherapy; CD137; Co stimulation; Cytotoxic T lymphocyte A4; Melanoma; Peptide vaccine; Tumor immunotherapy

Indexed keywords

CANVAXIN; CYCLOPHOSPHAMIDE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; FLUDARABINE; GLYCOPROTEIN GP 100; HEAT SHOCK PROTEIN; IMMUNOLOGICAL ADJUVANT; INTERLEUKIN 2; IPILIMUMAB; MONOCLONAL ANTIBODY; RECOMBINANT ANTIGEN; VACCINE;

ACTIVE IMMUNIZATION; CANCER IMMUNOTHERAPY; CANCER INHIBITION; CELL LYSATE; CELL THERAPY; CELL TRANSFER; CLINICAL STUDY; CLINICAL TRIAL; COHORT ANALYSIS; DRUG DOSE ESCALATION; DRUG MECHANISM; DRUG MEGADOSE; ERADICATION THERAPY; HUMAN; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOTOXICITY; LYMPHOCYTE ACTIVATION; MELANOMA; METASTASIS; PASSIVE IMMUNIZATION; REVIEW; T LYMPHOCYTE; TUMOR CELL; VIRUS RECOMBINANT;

ANIMALS; ANTIGENS, CD; ANTIGENS, DIFFERENTIATION; HUMANS; IMMUNIZATION, PASSIVE; IMMUNOTHERAPY; IMMUNOTHERAPY, ACTIVE; MELANOMA;

EID: 34047157600     PISSN: 14648431     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (106)

1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ: Cancer statistics, 2006. CA Cancer J Clin (2006) 56(2):106-130.
2. Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, Urist M, McMasters KM, Ross MI, Kirkwood JM, Aktkins MB et al: Prognostic factors analysis of 17,600 melanoma patients: Validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol (2001) 19(16):3622-3634.
3. Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, Fleming ID, Gerschenwald JE, Houghton A Jr, Kirkwood JM, McMasters KM et al: Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol (2001) 19(16):3635-3648. • This paper presents the latest AJCC staging system for malignant melanoma.
4. Wheatley K, Ives N, Hancock B, Gore M, Eggermont A, Suciu S: Does adjuvant interferon-α for high-risk melanoma provide a worthwhile benefit? A meta-analysis of the randomised trials. Cancer Treat Rev (2003) 29(4):241-252.
5. Crosby T, Fish R, Coles B, Mason MD: Systemic treatments for metastatic cutaneous melanoma. Cochrane Database Syst Rev (2000) 2:CD001215.
6. Falkson CI, Ibrahim J, Kirkwood JM, Coates AS, Atkins MB, Blum RH: Phase III trial of dacarbazine versus dacarbazine with interferon α-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon α-2b and tamoxifen in patients with metastatic malignant melanoma: An Eastern Cooperative Oncology Group study. J Clin Oncol (1998) 16(5):1743-1751.
7. Chapman PB, Einhorn LH, Meyers ML, Saxman S, Destro AN, Panageas KS, Begg CB, Agarwala SS, Schuchter LM, Ernstoff MS, Houghton AN, Kirkwood JM: Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol (1999) 17(9):2745-2751.
8. Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Seipp CA, Einhorn JH, White DE, Steinberg SM: Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon α-2b. J Clin Oncol (1999) 17(3):968-975.
9. Keilholz U, Punt CJ, Gore M, Kruit W, Patel P, Lienard D, Thomas J, Proebstle TM, Schmittel A, Schadendorf D, Velu T et al: Dacarbazine, cisplatin, and interferon-α-2b with or without interleukin-2 in metastatic melanoma: A randomized phase III trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group. J Clin Oncol (2005) 23(27):6747-6755.
10. Boon T, Coulie PG, Van den Eynde BJ, van der Bruggen P: Human T cell responses against melanoma. Annu Rev Immunol (2006) 24:175-208.
11. Rosenberg SA, Yang JC, Restifo NP: Cancer immunotherapy: Moving beyond current vaccines. Nat Med (2004) 10(9):909-915. • Rosenberg et al review their experience of over 400 patients treated with cancer vaccines at the National Cancer Institute. This is the largest singleinstitution experience of vaccines in cancer therapy.
12. Rosenberg SA, Sherry RM, Morton KE, Scharfman WJ, Yang JC, Topalian SL, Royal RE, Kammula U, Restifo NP, Hughes MS, Schwartzentruber D 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 (2005) 175(9):6169-6176. • This paper presents an important observation suggesting that not all tetramer-positive CTLs generated by cancer vaccines are necessarily correlative to clinical outcomes.
13. Pittet MJ, Valmori D, Dunbar PR, Speiser DE, Lienard D, Lejeune F, Fleischhauer K, Cerundolo V, Cerottini JC, Romero P: High frequencies of naive Melan-A/MART-1-specific CD8+ T cells in a large proportion of human histocompatibility leukocyte antigen (HLA)-A2 individuals. J Exp Med (1999) 190(5):705-715.
14. Bownds S, Tong-On P, Rosenberg SA, Parkhurst M: Induction of tumor-reactive cytotoxic T-lymphocytes using a peptide from NY-ESO-1 modified at the carboxy-terminus to enhance HLA-A2.1 binding affinity and stability in solution. J Immunother (2001) 24(1):1-9.
15. Parkhurst MR, Sallgaller ML, Southwood S, Robbins PF, Sette A, Rosenberg SA, Kawakami Y: Improved induction of melanomareactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0201-binding residues. J Immunol (1996) 157(6):2539-2548.
16. Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Topalian SL, Sherry RM, Restifo NP, Wunderlich JR, Seipp CA, Rogers-Freezer L, Morton KE et al: Recombinant fowlpox viruses encoding the anchor-modified gp100 melanoma antigen can generate antitumor immune responses in patients with metastatic melanoma. Clin Cancer Res (2003) 9(8):2973-2980.
17. van Baren N, Bonnet MC, Dreno B, Khammari A, Dorval T, Piperno-Neumann S, Lienard D, Speiser D, Marchand M, Brichard VG, Escudier B et al: Tumoral and immunologic response after vaccination of melanoma patients with an ALVAC virus encoding MAGE antigens recognized by T cells. J Clin Oncol (2005) 23(35):9008-9021.
18. Karanikas V, Lurquin C, Colau D, van Baren N, De Smet C, Lethe B, Connerotte T, Corbiere V, Demoitie MA, Lienard D, Dreno B et al: Monoclonal anti-MAGE-3 CTL responses in melanoma patients displaying tumor regression after vaccination with a recombinant canarypox virus. J Immunol (2003) 171(9):4898-4904.
19. Germeau C, Ma W, Schiavetti F, Lurquin P, Henry E, Vigneron N, Brasseur F, Lethé B, De Plaen E, Velu T, Boon T, Coulie PG: High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens. J Exp Med (2005) 201(2):241-248.
20. Lurquin C, Lethé B, De Plaen E, Corbière V, Théate I, van Baren N, Coulie PG, Boon T: Contrasting frequencies of antitumor and antivaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigen. J Exp Med (2005) 201(2):249-257.
21. Sakaguchi S: Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol (2005) 6(4):345-352. • This paper provides a critical description of a subset of helper T-lymphocytes expressing immunosuppressive function/tolerance against cancer antigens.
22. Ichikawa M, Chen L: Role of B7-H1 and B7-H4 molecules in down-regulating effector phase of T-cell immunity: Novel cancer escaping mechanisms. Front Biosci (2005) 10:2856-2860.
23. Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, Kavanaugh D, Carbone DP: Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med (1996) 2(10):1096-1103. • This study provided the first suggestion that there may be an interaction between angiogenesis and immunity.
24. Zou W: Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer (2005) 5(4):263-274.
25. Wilcox RA, Chen L: Immunotherapy of human papillomavirus-associated malignancies and the challenges posed by T-cell tolerance. Front Biosci (2002) 7:D853-D871.
26. Khong HT, Restifo NP: Natural selection of tumor variants in the generation of "tumor escape" phenotypes. Nat Immunol (2002) 3(11):999-1005.
27. Keilholz U, Weber J, Finke JH, Gabrilovich GI, Kast WM, Disis ML, Kirkwood JM, Scheibenbogen C, Schlom J, Maino VC, Lyerly HK et al: Immunologic monitoring of cancer vaccine therapy: Results of a workshop sponsored by the Society for Biological Therapy. J Immunother (2002) 25(2):97-138. • This paper provides a consensus statement on the state of the art methods for immune response monitoring in cancer immunotherapy clinical trials.
28. Smith CL, Dunbar PR, Mirza F, Palmowski MJ, Shepherd D, Gilbert SC, Coulie P, Schneider J, Hoffman E, Hawkins R, Harris AL, Cerundolo V: Recombinant modified vaccinia Ankara primes functionally activated CTL specific for a melanoma tumor antigen epitope in melanoma patients with a high risk of disease recurrence. Int J Cancer (2005) 113(2):259- 266.
29. Schultz J, Pavlovic J, Strack B, Nawrath M, Moelling K: Long-lasting anti-metastatic efficiency of interleukin 12-encoding plasmid DNA. Hum Gene Ther (1999) 10(3):407-417.
30. Heinzerling L, Burg G, Dummer R, Maier T, Oberholzer PA, Schultz J, Elzaouk L, Pavlovic J, Moelling K: Intratumoral injection of DNA encoding human interleukin 12 into patients with metastatic melanoma: Clinical efficacy. Hum Gene Ther (2005) 16(1):35-48.
31. Vaishampayan U, Abrams J, Darrah D, Jones V, Mitchell MS: Active immunotherapy of metastatic melanoma with allogeneic melanoma lysates and interferon α. Clin Cancer Res (2002) 8(12):3696-3701.
32. Hersey P, Coates AS, McCarthy WH, Thompson JF, Sillar RW, McLeod R, Gill PG, Coventry BJ, McMullen A, Dillon H, Simes RJ: Adjuvant immunotherapy of patients with high-risk melanoma using vaccinia viral lysates of melanoma: Results of a randomized trial. J Clin Oncol (2002) 20(20):4181-4190.
33. Belli F, Testori A, Rivoltini L, Maio M, Andreola G, Sertoli MR, Gallino G, Piris A, Cattelan A, Lazzari I, Carrabba M et al: Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: Clinical and immunologic findings. J Clin Oncol (2002) 20(20):4169-4180.
34. Chang AE, Li Q, Bishop DK, Normolle DP, Redman BD, Nickoloff BJ: Immunogenetic therapy of human melanoma utilizing autologous tumor cells transduced to secrete granulocyte-macrophage colony-stimulating factor. Hum Gene Ther (2000) 11(6):839-850.
35. Moller P, Moller H, Sun Y, Dorbic T, Henz BM, Wittig B, Schadendorf D: Increased non-major histocompatibility complex-restricted lytic activity in melanoma patients vaccinated with cytokine gene-transfected autologous tumor cells. Cancer Gene Ther (2000) 7(7):976-984.
36. Lotem M, Peretz T, Drize O, Gimmon Z, Ad El D, Weitzen R, Goldberg H, Ben David I, Prus D, Hamburger T, Shiloni E: Autologous cell vaccine as a post operative adjuvant treatment for high-risk melanoma patients (AJCC stages III and IV). The new American Joint Committee on Cancer. Br J Cancer (2002) 86(10):1534-1539.
37. Osanto S, Schiphorst PP, Weill NI, Dijkstra N, Van Wees A, Brouwenstein N, Vaessen N, Van Krieken JH, Hermans J, Cleton FJ, Schrier PI: Vaccination of melanoma patients with an allogeneic, genetically modified interleukin 2-producing melanoma cell line. Hum Gene Ther (2000) 11(5):739-750.
38. Nagayama H, Sato K, Morishita M, Uchimaru K, Oyaizu N, Inazawa T, Yamasaki T, Enomoto M, Nakaoka T, Nakamura T, Maekawa T et al: Results of a phase I clinical study using autologous tumour lysate-pulsed monocyte-derived mature dendritic cell vaccinations for stage IV malignant melanoma patients combined with low dose interleukin-2. Melanoma Res (2003) 13(5):521-530.
39. Banchereau J, Ueno H, Dhodapkar M, Connolly J, Finholt JP, Klechevsky E, Blanck JP, Johnston DA, Palucka AK, Fay J: Immune and clinical outcomes in patients with stage IV melanoma vaccinated with peptide-pulsed dendritic cells derived from CD34+ progenitors and activated with type I interferon. J Immunother (2005) 28(5):505-516.
40. Palucka AK, Dhodapkar MV, Paczesny S, Burkeholder S, Wittkowski KM, Steinman RM, Fay J, Banchereau J: Single injection of CD34+ progenitor-derived dendritic cell vaccine can lead to induction of Tcell immunity in patients with stage IV melanoma. J Immunother (2003) 26(5):432-439.
41. Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N, Rolland A, Taquet S, Coquery S, Wittkowski KM, Bhardwaj N, Pineiro L et al: Immune and clinical responses in patients with metastatic melanoma to CD34+ progenitor-derived dendritic cell vaccine. Cancer Res (2001) 61(17):6451-6458.
42. Panelli MC, Wunderlich J, Jeffries J, Wang E, Mixon A, Rosenberg SA, Marincola FM: Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100. J Immunother (2000) 23(4):487-498.
43. Haenssle HA, Krause SW, Emmert S, Zutt M, Kretschmer L, Schmidberger H, Andreesen R, Soruri A: Hybrid cell vaccination in metastatic melanoma: Clinical and immunologic results of a phase I/II study. J Immunother (2004) 27(2):147-155.
44. Bystryn JC, Zeleniuch-Jacquotte A, Oratz R, Shapiro RL, Harris MN, Roses DF: Double-blind trial of a polyvalent, shed-antigen, melanoma vaccine. Clin Cancer Res (2001) 7(7):1882-1887.
45. Morton DL, Hsueh EC, Essner R, Foshag LJ, O'Day SJ, Bilchik A, Gupta RK, Hoon DS, Ravindranath M, Nizze JA, Gammons G et al: Prolonged survival of patients receiving active immunotherapy with Canvaxin therapeutic polyvalent vaccine after complete resection of melanoma metastatic to regional lymph nodes. Ann Surg (2002) 236(4):438-448. • This paper presents the first data suggesting the benefit of a cancer vaccine in the treatment of patients with melanoma; however, the follow-up phase III clinical trial did not confirm these observations.
46. Hsueh EC, Essner R, Foshag LJ, Ollila DW, Gammon G, O'Day SJ, Boasberg PD, Stern SL, Ye X, Morton DL: Prolonged survival after complete resection of disseminated melanoma and active immunotherapy with a therapeutic cancer vaccine. J Clin Oncol (2002) 20(23):4549-4554.
47. CancerVax Corp: Data and Safety Monitoring Board Recommends Discontinuation of Canvaxin™ Phase 3 Clinical Trial for Patients with Stage III Melanoma. Press Release (2005): October 03.
48. Spitler LE, Grossbard ML, Ernstoff MS, Silver G, Jacobs M, Hayes FA, Soong SJ: Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor. J Clin Oncol (2000) 18(8):1614-1621. • This was the first report that a cytokine other than IFN may be of clinical benefit in adjuvant therapy of resected, advanced-stage melanoma. This therapy is currently being tested in a placebo controlled phase III clinical trial (E4697).
49. Kirkwood JM, Moschos S, Wang W: Strategies for the development of more effective adjuvant therapy of melanoma: Current and future explorations of antibodies, cytokines, vaccines, and combinations. Clin Cancer Res (2006) 12(7 Pt 2):2331s-2336s.
50. Dudley ME, Rosenberg SA: Adoptive-cell-transfer therapy for the treatment of patients with cancer. Nat Rev Cancer (2003) 3(9):666-675.
51. Yee C, Thompson JA, Byrd D, Riddell SR, Roche P, Celis E, Greenberg PD: 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 (2002) 99(25):16168-16173. • This study provides clear evidence that tumor-specific CTLs are capable of tumor destruction in humans.
52. Lotze MT, Rosenberg SA: Results of clinical trials with the administration of interleukin 2 and adoptive immunotherapy with activated cells in patients with cancer. Immunobiology (1986) 172(3-5):420- 437.
53. Mule JJ, Ettinghausen SE, Spiess PJ, Shu S, Rosenberg SA: Antitumor efficacy of lymphokine-activated killer cells and recombinant interleukin-2 in vivo: Survival benefit and mechanisms of tumor escape in mice undergoing immunotherapy. Cancer Res (1986) 46(2):676-683.
54. Papa MZ, Mule JJ, Rosenberg SA: Antitumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo: Successful immunotherapy of established pulmonary metastases from weakly immunogenic and nonimmunogenic murine tumors of three district histological types. Cancer Res (1986) 46(10):4973-4978.
55. Cheever MA, Greenberg PD, Fefer A: Specificity of adoptive chemoimmunotherapy of established syngeneic tumors. J Immunol (1980) 125(2):711-714.
56. North RJ: Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells. J Exp Med (1982) 155(4):1063-1074.
57. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR et al: Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science (2002) 298(5594):850-854.
58. Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, Royal RE, Kammula U, White DE, Mavroukakis SA, Rogers LJ et al: Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol (2005) 23(10):2346-2357. • In this study, approximately 50% of patients with metastatic melanoma achieved a clinical response following ACT and lymphodepleting chemotherapy. Long-term persistence of adoptively transferred cells was observed.
59. Gattinoni L, Finkelstein SE, Klebanoff CA, Antony PA, Palmer DC, Spiess PJ, Hwang LN, Yu Z, Wrzesinski C, Heimann DM, Surh CD et al: Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J Exp Med (2005) 202(7):907-912.
60. Sakaguchi S: Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol (2004) 22:531-562.
61. Zhang H, Chua KS, Guimond M, Kapoor V, Brown MV, Fleisher TA, Long LM, Bernstein D, Hill BJ, Douek DC, Berzofsky JA et al: Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat Med (2005) 11(11):1238-1243.
62. hi Foxp3+ regulatory T cells in cancer patients. Blood (2006) 107(6):2409-2414.
63. Rosenberg SA, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE: Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. J Am Med Assoc (1994) 271(12):907-913.
64. Lanzavecchia A, Sallusto F: Progressive differentiation and selection of the fittest in the immune response. Nat Rev Immunol (2002) 2(12):982-987.
65. Appay V, Dunbar PR, Callan M, Klenerman P, Gillespie GM, Pagagno L, Ogg GS, King A, Lechner F, Spina CA, Little S et al: Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat Med (2002) 8(4):379-385.
66. Gattinoni L, Klebanoff CA, Palmer DC, Wrzesinski C, Kerstann K, Yu Z, Finkelstein SE, Theoret MR, Rosenberg SA, Restifo NP: Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells. J Clin Invest (2005) 115(6):1616-1626. • This study demonstrated that fully differentiated effector cells, while exhibiting full effector function in vitro, are largely senescent and unable to mediate tumor regression upon adoptive transfer into tumor-bearing mice.
67. Dudley ME, Wunderlich JR, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry RM, Marincola FM, Leitman SF, Seipp CA, Rogers-Freezer L et al: A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. J Immunother (2002) 25(3):243-251.
68. Hendriks J, Gravestein LA, Tesselaar K, van Lier RA, Schumacher TN, Borst J: CD27 is required for generation and long-term maintenance of T cell immunity. Nat Immunol (2000) 1(5):433-440.
69. Hendriks J, Xiao Y, Borst J: CD27 promotes survival of activated T cells and complements CD28 in generation and establishment of the effector T cell pool. J Exp Med (2003) 198(9):1369-1380.
70. Powell DJ Jr, Dudley ME, Robbins PF, Rosenberg SA: Transition of late-stage effector T cells to CD27+ CD28+ tumor-reactive effector memory T cells in humans after adoptive cell transfer therapy. Blood (2005) 105(1):241-250.
71. Huang J, Kerstann KW, Ahmadzadeh M, Li YF, El-Gamil M, Rosenberg SA, Robbins PF: Modulation by IL-2 of CD70 and CD27 expression on CD8+ T cells: Importance for the therapeutic effectiveness of cell transfer immunotherapy. J Immunol (2006) 176(12):7726-7735.
72. Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z et al: Cancer regression in patients after transfer of genetically engineered lymphocytes. Science (2006) 314(5796):126-129.
73. Chambers CA, Kuhns MS, Egen JG, Allison JP: CTLA-4-mediated inhibition in regulation of T cell responses: Mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol (2001) 19:565-594.
74. Waterhouse P, Penninger JM, Timms E, Wakeham A, Shahinian A, Lee KP, Thompson CB, Griesser H, Mak TW: Lymphoproliferative disorders with early lethality in mice deficient in CTLA-4. Science (1995) 270(5238):985-988.
75. Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH: Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity (1995) 3(5):541-547.
76. Waterhouse P, Bachmann MF, Penninger JM, Ohashi PS, Mak TW: Normal thymic selection, normal viability and decreased lymphoproliferation in T cell receptor-transgenic CTLA-4-deficient mice. Eur J Immunol (1997) 27(8):1887-1892.
77. Chambers CA, Sullivan TJ, Truong T, Allison JP: Secondary but not primary T cell responses are enhanced in CTLA-4-deficient CD8+ T cells. Eur J Immunol (1998) 28(10):3137-3143.
78. van Elsas A, Hurwitz AA, Allison JP: Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med (1999) 190(3):355-366.
79. Hodi FS, Mihm MC, Soiffer RJ, Haluska FG, Butler M, Seiden MV, Davis T, Henry-Spires R, MacRae S, Willman A, Padera R et al: Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci USA (2003) 100(8):4712-4717.
80. Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, Restifo NP, Haworth LR, Seipp CA, Freezer LJ, Morton KE 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 (2003) 100(14):8372-8377. • This landmark study demonstrated clinical responses, associated with autoimmunity, in melanoma patients receiving anti-CTLA-4 therapy.
81. Attia P, Phan GQ, Maker AV, Robinson MR, Quezado MM, Yang JC, Sherry RM, Topalian SL, Kammula US, Royal RE, Restifo NP et al: Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol (2005) 23(25):6043-6053. • Autoimmunity following CTLA-4 blockade was clearly demonstrated to be associated with tumor regression and may be mediated by CD4+ T-cells.
82. Sanderson K, Scotland R, Lee P, Liu D, Groshen S, Snively J, Sian S, Nichol G, Davis T, Keler T, Yellin M et al: Autoimmunity in a phase I trial of a fully human anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody with multiple melanoma peptides and Montanide ISA 51 for patients with resected stages III and IV melanoma. J Clin Oncol (2005) 23(4):741- 750.
83. Maker AV, Phan GQ, Attia P, Yang JC, Sherry RM, Topalian SL, Kammula US, Royal RE, Haworth LR, Levy C, Kleiner D et al: Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: A phase I/II study. Ann Surg Oncol (2005) 12(12):1005-1016.
84. Ribas A, Camacho LH, Lopez-Berestein G, Pavlov D, Bulanhagui CA, Millham R, Comin-Anduix B, Reuben JM, Seja E, Parker CA, Sharma A et al: Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. J Clin Oncol (2005) 23(35):8968-8977.
85. Tang Q, Boden EK, Henriksen KJ, Bour-Jordan H, Bi M, Bluestone JA: Distinct roles of CTLA-4 and TGF-β in CD4+CD25+ regulatory T cell function. Eur J Immunol (2004) 34(11):2996-3005.
86. Read S, Malmstrom V, Powrie F: Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25+CD4+ regulatory cells that control intestinal inflammation. J Exp Med (2000) 192(2):295-302.
87. Sutmuller RP, van Duivenvoorde LM, van Elsas A, Schumacher TN, Wildenberg ME, Allison JP, Toes RE, Offringa R, Melief CJ: Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25+ regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J Exp Med (2001) 194(6):823-832.
88. Watts TH: TNF/TNFR family members in costimulation of T cell responses. Annu Rev Immunol (2005) 23:23-68.
89. Greenwald RJ, Freeman GJ, Sharpe AH: The B7 family revisited. Annu Rev Immunol (2005) 23:515-548.
90. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA et al: Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat Med (2002) 8(8):793-800. • This study clearly illustrates that malignant tumors express molecules that directly downregulate CTL function by promoting apoptosis.
91. Thompson RH, Kuntz SM, Leibovich BC, Dong H, Lohse CM, Webster WS, Sengupta S, Frank I, Parker AS, Zincke H, Blute ML et al: Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res (2006) 66(7):3381-3385.
92. Thompson RH, Gillett MD, Cheville JC, Lohse CM, Dong H, Webster WS, Krejci KG, Lobo JR, Sengupta S, Chen L, Zincke H et al: Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci USA (2004) 101(49):17174-17179.
93. Hirano F, Kaneko K, Tamura H, Dong H, Wang S, Ichikawa M, Rietz C, Flies DB, Lau JS, Zhu G, Tamada K et al: Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res (2005) 65(3):1089-1096.
94. Liu X, Gao JX, Wen J, Yin L, Li O, Zuo T, Gajewski TF, Fu YX, Zheng P, Liu Y: B7DC/PDL2 promotes tumor immunity by a PD-1-independent mechanism. J Exp Med (2003) 197(12):1721-1730.
95. Nguyen LT, Radhakrishnan S, Ciric B, Tamada K, Shin T, Pardoll DM, Chen L, Rodriguez M, Pease LR: Cross-linking the B7 family molecule B7-DC directly activates immune functions of dendritic cells. J Exp Med (2002) 196(10):1393-1398.
96. Radhakrishnan S, Celis E, Pease LR: B7-DC cross-linking restores antigen uptake and augments antigen-presenting cell function by matured dendritic cells. Proc Natl Acad Sci USA (2005) 102(32):11438- 11443.
97. Radhakrishnan S, Nguyen LT, Ciric B, Flies D, Van Keulen VP, Tamada K, Chen L, Rodriguez M, Pease LR: Immunotherapeutic potential of B7-DC (PD-L2) cross-linking antibody in conferring antitumor immunity. Cancer Res (2004) 64(14):4965-4972.
98. Tamada K, Chen L: Renewed interest in cancer immunotherapy with the tumor necrosis factor superfamily molecules. Cancer Immunol Immunother (2006) 55(4):355-362.
99. Wilcox RA, Flies DB, Zhu G, Johnson AJ, Tamada K, Chapoval AI, Strome SE, Pease LR, Chen L: Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors. J Clin Invest (2002) 109(5):651-659.
100. Melero I, Shuford WW, Newby SA, Aruffo A, Ledbetter JA, Hellstrom KE, Mittler RS, Chen L: Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat Med (1997) 3(6):682-685.
101. Wilcox RA, Chapoval AI, Gorski KS, Otsuji M, Shin T, Flies DB, Tamada K, Mittler RS, Tsuchiya H, Pardoll DM, Chen L: Cutting edge: Expression of functional CD137 receptor by dendritic cells. J Immunol (2002) 168(9):4262-4267.
102. Wilcox RA, Tamada K, Strome SE, Chen L: Signaling through NK cell-associated CD137 promotes both helper function for CD8+ cytolytic T cells and responsiveness to IL-2 but not cytolytic activity. J Immunol (2002) 169(8):4230-4236.
103. Wilcox RA, Flies DB, Wang H, Tamada K, Johnson AJ, Pease LR, Rodriguez M, Guo Y, Chen L: Impaired infiltration of tumor-specific cytolytic T cells in the absence of interferon-γ despite their normal maturation in lymphoid organs during CD137 monoclonal antibody therapy. Cancer Res (2002) 62(15):4413-4418.
104. Wilcox RA, Tamada K, Flies DB, Zhu G, Chapoval AI, Blazar BR, Kast WM, Chen L: Ligation of CD137 receptor prevents and reverses established anergy of CD8+ cytolytic T lymphocytes in vivo. Blood (2004) 103(1):177-184.
105. Tamada K, Shimozaki K, Chapoval AI, Zhu G, Sica G, Flies D, Boone T, Hsu H, Fu YX, Nagata S, Ni J et al: Modulation of T-cell-mediated immunity in tumor and graft-versus-host disease models through the LIGHT co-stimulatory pathway. Nat Med (2000) 6(3):283-289.
106. Yu P, Lee Y, Liu W, Chin RK, Wang J, Wang Y, Schietinger A, Philip M, Schreiber H, Fu YX: Priming of naive T cells inside tumors leads to eradication of established tumors. Nat Immunol (2004) 5(2):141-149.