Melanoma pp 141-156 | Cite as

Immunotherapy of Advanced Melanoma Directed at Specific Antigens

  • Stanley P. L. Leong
  • Suyu Shu
Part of the Current Clinical Oncology book series (CCO)


Since the description of melanoma in 1787, its biological behavior has suggested that the immune system may play a significant role in its interaction with melanoma. Several lines of evidence may support this hypothesis: (i) in documented cases of children with spontaneous regression of cancer, melanoma has been found to be the cancer second in incidence to neuroblastoma (1); (ii) approximately 5% of patients with metastatic melanoma have an unknown primary suggesting that the primary melanoma may have regressed spontaneously (2,3); (iii)although widespread vitiligo-like leukoderma is an uncommon clinical entity, its clinical manifestation suggests that an immune mechanism may be the cause of destruction of both normal melanocytes and malignant melanoma (4); (iv) in superficial spreading melanoma, it is not infrequent to appreciate areas of regression with tumor-infiltrating lymphocytes (TILs). Lymphocytic infiltration of the primary tumor has been associated with a better prognosis than when the primary tumor is not infiltrated with lymphocytes (5-7); (v) although it is not a common finding, there are patients whose melanoma may remain dormant for over 20 yr after the diagnosis of the primary melanoma, who subsequently recur and die from melanoma (8). This may suggest tumor escape following a long period of host tumor interaction; and (vi) finally, the significantly increased incidence and poorer prognosis for melanoma developed in immunosuppressed renal transplant recipients (9) provides additional clinical evidence for the role of immune surveillance in the evolution of melanoma.


Metastatic Melanoma Adoptive Immunotherapy Active Specific Immunotherapy Iymph Node Autologous Melanoma Cell 
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  1. 1.
    Everson T, Cole W. Spontaneous Regression of Cancer. W.B. Saunders, Philadelphia, 1966.Google Scholar
  2. 2.
    Reintgen DS, McCarty KS, Woodard B, et al. Metastatic malignant melanoma with an unknown primary. Surg Gynecol Obstet 1983; 156: 335–340.PubMedGoogle Scholar
  3. 3.
    Nathanson L. Spontaneous regression of malignant melanoma: a review of the literature on incidence, clinical features, and possible mechanisms. Natl Cancer Inst Monogr 1989; 44.Google Scholar
  4. 4.
    Koh HK, Sober AJ, Nakagawa H, et al. Malignant melanoma and vitiligo-like leukoderma: an electron microscopic study. J Am Acad Dermatol 1983; 9: 696–708.PubMedGoogle Scholar
  5. 5.
    Smith J, Stehlin JS Jr. Spontaneous regression of primary malignant melanoma with regional metastases. Cancer 1965; 18: 1399.PubMedGoogle Scholar
  6. 6.
    Clark WH, Elder DE, DuPont G IV, et al. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst 1989; 81: 1893–1904.PubMedGoogle Scholar
  7. 7.
    Tefany FJ, Barnetson RS, Halliday GM, et al. Immunocytochemical analysis of the cellular infiltrate in primary regressing and non-regressing malignant melanoma. J Invest Dermatol 1991; 97: 197–202.PubMedGoogle Scholar
  8. 8.
    Briele HA, Beattie CW, Ronan SG, et al. Late recurrence of cutaneous melanoma. Arch Surg 1983; 118: 800–803.PubMedGoogle Scholar
  9. 9.
    Penn I. Immunosuppression and skin cancer. Clin Plast Surg 1980; 7: 361–368.PubMedGoogle Scholar
  10. 10.
    Mavligit GM, Hersh EM, McBride CM. Lymphocyte blastogenic responses to autochthonous viable and nonviable human tumor cells. J Natl Cancer Inst 1973; 51: 337–343.PubMedGoogle Scholar
  11. 11.
    Rossen RD, Crane MM, Morgan AC, et al. Circulating immune complexes and tumor cell cytotoxins as prognostic indicators in malignant melanoma: a prospective study of 53 patients. Cancer Res 1983; 43: 422–429.PubMedGoogle Scholar
  12. 12.
    Shiku H, Takahashi T, Resnick LA, et al. Cell surface antigens of human malignant melanoma. III. Recognition of autoantibodies with unusual characteristics. J Exp Med 1977; 145: 784–789.PubMedGoogle Scholar
  13. 13.
    Oettgen HF. Immunotherapy of cancer. N Engl J Med 1977; 297: 484–491.PubMedGoogle Scholar
  14. 14.
    Steffans T, Bajorin D, Houghton A. Immunotherapy with monoclonal antibodies in metastatic melanoma. World J Surg 1992; 16: 261–269.Google Scholar
  15. 15.
    Anichini A, Fossati G, Parmiani G. Clonal analysis of cytotoxic T-lymphocyte response to autologous human metastatic melanoma. Im J Cancer 1985; 35: 683–689.Google Scholar
  16. 16.
    Anichini A, Fossati G, Parmiani G. Heterogeneity of clones from a human metastatic melanoma detected by autologous cytotoxic T lymphocyte clones. J Exp Med 1986; 163: 215–220.PubMedGoogle Scholar
  17. 17.
    Anichini A, Mazzocchi A, Fossati G, et al. Cytotoxic T lymphocyte clones from peripheral blood and from tumor site detect intratumor heterogeneity of melanoma cells. Analysis of specificity and mechanisms of interaction. Jlmmunol 1989; 142: 3692–3701.Google Scholar
  18. 18.
    van der Bruggen P, Traversari C, Chomez P, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 1991; 254: 1643–1647.PubMedGoogle Scholar
  19. 19.
    Hersey P, Bindon C, Edwards A, et al. Induction of cytotoxic activity in human lymphocytes against autologous and allogeneic melanoma cells in vitro by culture with interleukin 2. Int J Cancer 1981; 28: 695–703.PubMedGoogle Scholar
  20. 20.
    Knuth A, Danowkis B, Oettgen HF, Old Li. T-cell-mediated cytotoxicity against autologous malignant melanoma: analysis with interleukin 2-dependent T-cell cultures. Proc Natl Acad Sci USA 1984; 81: 3511–3515.PubMedGoogle Scholar
  21. 21.
    Topalian S, Mull L, Rosenberg S. Growth and immunologic characteristics of lymphocytes infiltrating human tumors. Surg Forum 1986; 37: 390–391.Google Scholar
  22. 22.
    Muul LM, Spiess PJ, Director EP, et al. Identification of specific cytolytic immune responses against autologous tumor in humans bearing malignant melanoma. J Immunol 1987; 138: 989–995.PubMedGoogle Scholar
  23. 23.
    Rosenberg SA, Packard BS, Aebersold PM, et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report [see comments]. N Engl J Med 1988; 319: 1676–1680.PubMedGoogle Scholar
  24. 24.
    Crowley NJ, Darrow TL, Quinn-Allen MA, et al. MHC-restricted recognition of autologous melanoma by tumor-specific cytotoxic T cells. Evidence for restriction by a dominant HLA-A allele. Jlmmunol 1991; 146: 1692–1699.Google Scholar
  25. 25.
    Leong SPL, Granberry ME, Zhou YM, et al. Selection of cytotoxic T lymphocytes against autologous human melanoma from lymph nodes with metastatic melanoma using repeated in vitro sensitization Clin Exp Metastasis 1991; 9: 301–317.PubMedGoogle Scholar
  26. 26.
    Leong SPL, Zhou YM, Granberry ME, et al. Generation of cytotoxic effector cells against human melanoma. Cancer Immunol Immunother 1995; 40: 397–409.PubMedGoogle Scholar
  27. 27.
    Mukherji B, Wilhelm SA, Guha A, et al. Regulation of cellular immune response against autologous human melanoma. I. Evidence for cell-mediated suppression of in vitro cytotoxic immune response. J Immunol 1986; 136: 1888–1892.PubMedGoogle Scholar
  28. 28.
    Mukherj B, Nashed AL, Guha A, Ergin MT. Regulation of cellular immune response against autologous human melanoma. II. Mechanism of induction and specificity of suppression. J Immunol 1986; 136: 1893–1898.Google Scholar
  29. 29.
    Chakraborty NG, Twardzik DR, Sivanandham M, et al. Autologous melanoma-induced activation of regulatory T cells that suppress cytotoxic response. J Immunol 1990; 145: 2359–2364.PubMedGoogle Scholar
  30. 30.
    Hoon DS, Foshag LJ, Nizze AS, et al. Suppressor cell activity in a randomized trial of patients receiving active specific immunotherapy with melanoma cell vaccine and low dosages of cyclophosphamide. Cancer Res 1990; 50: 5358–5364.PubMedGoogle Scholar
  31. 31.
    Grin-Jorgensen CM, Rigel DS, Friedman R.I. The worldwide incidence of malignant melanoma. In: Balch C, Houghton A, Milton G, et al., eds., Cutaneous Melanoma. J.B. Lippincott, Philadelphia, 1992, p. 27.Google Scholar
  32. 32.
    Berd D, Maguire H Jr, Mastrangelo M. Induction of cell-mediated immunity to autologous melanoma cells and regression of metastases after treatment with a melanoma cell vaccine preceded by cyclophosphamide. Cancer Res 1986; 46: 2572–2577.PubMedGoogle Scholar
  33. 33.
    Leong SP, Enders-Zohr P, Zhou YM, et al. Recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) and autologous melanoma vaccine mediate tumor regression in patients with metastatic melanoma. J Immunother 1999; 22: 166–174.PubMedGoogle Scholar
  34. 34.
    Livingston PO, Kaelin K, Pinsky CM, et al. The serologic response of patients with stage II melanoma to allogeneic melanoma cell vaccines. Cancer 1985; 56: 2194–2200.PubMedGoogle Scholar
  35. 35.
    Morton DL, Foshag LJ, Hoon DS, et al. Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine [published erratum appears in Ann Surg 1993 Mar; 217(3): 309]. Ann Surg 1992; 216: 463–482.PubMedGoogle Scholar
  36. 36.
    Vadhan-Raj S, Cordon-Cardo C, Carswell E, et al. Phase I trial of a mouse monoclonal antibody against GD3 ganglioside in patients with melanoma: induction of inflammatory responses at tumor sites. J Clin Oncol 1988; 6: 1636–1648.PubMedGoogle Scholar
  37. 37.
    Livingston PO, Natoli EJ, Calves MJ, et al. Vaccines containing purified GM2 ganglioside elicit GM2 antibodies in melanoma patients. Proc Nati Acad Sci USA 1987; 84: 2911–2915.Google Scholar
  38. 38.
    Bystryn JC. Immunogenicity and clinical activity of a polyvalent melanoma antigen vaccine prepared from shed antigens. Ann NYAcad Sci 1993; 690: 190–203.Google Scholar
  39. 39.
    Mitchell MS, Harel W, Kempf RA, et al. Active-specific immunotherapy for melanoma. J Clin Oncol 1990; 8: 856–869.PubMedGoogle Scholar
  40. 40.
    Hersey P. Evaluation of vaccinia viral lysates as therapeutic vaccines in the treatment of melanoma. Ann NYAcad Sci 1993; 690: 167–177.Google Scholar
  41. 41.
    Wallack M, Muthukumaran S, Whooley B, et al. Favorable clinical responses in subsets of patients from a randomized, multi-institutional melanoma vaccine trial. Ann Surg Oncol 1995; 3: 110–117.Google Scholar
  42. 42.
    Giacomini P, Veglia F, Cordiali Fei P, et al. Level of a membrane-bound high-molecular-weight melanoma-associated antigen and a cytoplasmic melanoma-associated antigen in surgically removed tissues and in sera from patients with melanoma. Cancer Res 1984; 44: 1281–1287.PubMedGoogle Scholar
  43. 43.
    Ahn SS, Irie RF, Weisenburger TH, et al. Humoral immune response to intralymphatic immunotherapy for disseminated melanoma: correlation with clinical response. Surgery 1982; 92: 362–367.PubMedGoogle Scholar
  44. 44.
    Berd D, Maguire JR. Potentiation of human cell-mediated and humoral immunity by low-dose cyclophosphamide. Cancer Res 1984; 44: 5439–5443.PubMedGoogle Scholar
  45. 45.
    Estin C, Stevenson U, Plowman G, et al. Recombinant vaccinia virus vaccine against the human melanoma antigen p97 for use in immunotherapy. Proc Natl Acad Sci USA 1986; 83: 1261–1265.Google Scholar
  46. 46.
    Cheung NK, Lazarus H, Miraldi FD, et al. Ganglioside GD2 specific monoclonal antibody 3F8: a phase I study in patients with neuroblastoma and malignant melanoma [see comments]. J Clin Oncol 1987; 5: 1430–1440.PubMedGoogle Scholar
  47. 47.
    Berd D, Maguire H Jr, McCue P, et al. Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients. J Clin Oncol 1990; 8: 1858–1867.PubMedGoogle Scholar
  48. 48.
    Berd D, Maguire HC Jr, McCue P, et al. Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients. J Clin Oncol 1990; 8: 1858–1867.PubMedGoogle Scholar
  49. 49.
    Mittelman A, Chen ZJ, Kageshita T, et al. Active specific immunotherapy in patients with melanoma. A clinical trial with mouse antiidiotypic monoclonal antibodies elicited with syngeneic anti-high-molecular-weight-melanoma-associated antigen monoclonal antibodies [published erratum appears in J Clin Invest 1991 Feb; 87(2): 757]. J Clin Invest 1990; 86: 2136–2144.PubMedGoogle Scholar
  50. 50.
    Mittelman A, Chen ZJ, Yang H, et al. Human high molecular weight melanoma-associated antigen (HMW-MAA) mimicry by mouse anti-idiotypic monoclonal antibody MK2–23: induction of humoral anti-HMW-MAA immunity and prolongation of survival in patients with stage IV melanoma. Proc Natl Acad Sci USA 1992; 89: 466–470.PubMedGoogle Scholar
  51. 51.
    Mitchell MS, Harel W, Kan-Mitchell J, et al. Active specific immunotherapy of melanoma with allogeneic cell lysates. Rationale, results, and possible mechanisms of action. Ann NY Acad Sci 1993; 690: 153–166.PubMedGoogle Scholar
  52. 52.
    Livingston P, Wong G, Adluri S, et al. A randomized trial of adjuvant vaccination with BCG versus BCG plus the melanoma ganglioside GM2 in patients with AJCC stage III melanoma. Ann NYAcad Sci 1993; 690: 204–213.Google Scholar
  53. 53.
    Goodman G, Hellstrom I, Hu S, et al. Phase I trial of a melanoma vaccine expressing the p97 antigen [abstract]. Proc Natl Acad Sci USA 15E, 83: 1052–1056.Google Scholar
  54. 54.
    Chapman P, Livinston P, Morrison M, et al. Use of BEC2 anti-idiotypic monoclonal antibody (Mab) to induce antibodies against GD3 ganglioside in melanoma patients [abstract]. Proc Am Soc Clin Oncol 1993; 12: 388.Google Scholar
  55. 55.
    Rosenberg SA, Yang JC, Schwartzentruber DJ, et al. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma [see comments]. Nat Med 1998; 4: 321–327.PubMedGoogle Scholar
  56. 56.
    Shu SY, Chou T, Rosenberg SA. Generation from tumor-bearing mice of lymphocytes with in vivo therapeutic efficacy. J Immunol 1987; 139: 295–304.PubMedGoogle Scholar
  57. 57.
    Taniguchi T, Matsui H, Fujita T, et al. Structure and expression of a cloned cDNA for human interleukin-2. Nature 1983; 302: 305–310.PubMedGoogle Scholar
  58. 58.
    Mule JJ, Shu S, Schwarz SL, et al. Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2. Science 1984; 225: 1487–1489.PubMedGoogle Scholar
  59. 59.
    Rosenberg SA, Lotze MT, Muul LM, et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 1987; 316: 889–897.PubMedGoogle Scholar
  60. 60.
    Grimm EA, Mazumder A, Zhang HZ, et al. Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med 1982; 155: 1823–1841.PubMedGoogle Scholar
  61. 61.
    Grimm EA, Robb RJ, Roth JA, et al. Lymphokine-activated killer cell phenomenon. III. Evidence that IL-2 is sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer cells. J Exp Med 1983; 158: 1356–1361.PubMedGoogle Scholar
  62. 62.
    Schoof DD, Gramolini BA, Davidson DL, et al. Adoptive immunotherapy of human cancer using low-dose recombinant interleukin 2 and lymphokine-activated killer cells. Cancer Res 1988; 48: 5007–5010.PubMedGoogle Scholar
  63. 63.
    Dutcher JP, Creekmore S, Weiss GR, et al. A phase II study of interleukin-2 and lymphokine-activated killer cells in patients with metastatic malignant melanoma. J Clin Oncol 1989; 7: 477–485.PubMedGoogle Scholar
  64. 64.
    Bar MH, Sznol M, Atkins MB, et al. Metastatic malignant melanoma treated with combined bolus and continuous infusion interleukin-2 and lymphokine-activated killer cells [see comments]. J Clin Oncol 1990; 8: 1138–1147.PubMedGoogle Scholar
  65. 65.
    Dutcher JP, Gaynor ER, Boldt DH, et al. A phase II study of high-dose continuous infusion interleukin-2 with lymphokine-activated killer cells in patients with metastatic melanoma. J Clin Oncol 1991; 9: 641–648.PubMedGoogle Scholar
  66. 66.
    Atkins MB, Gould JA, Allegretta M, et al. Phase I evaluation of recombinant interleukin-2 in patients with advanced malignant disease. J Clin Oncol 1986; 4: 1380–1391.PubMedGoogle Scholar
  67. 67.
    Lotze MT, Chang AE, Seipp CA, et al. High-dose recombinant interleukin 2 in the treatment of patients with disseminated cancer. Responses, treatment-related morbidity, and histologic findings. JAMA 1986; 256: 3117–3124.PubMedGoogle Scholar
  68. 68.
    Mitchell MS, Kempf RA, Harel W, et al. Effectiveness and tolerability of low-dose cyclophosphamide and low-dose intravenous interleukin-2 in disseminated melanoma [corrected]. [published erratum appears in J Clin Oncol 1988 Jun; 6(6): 1067]. J Clin Oncol 1988; 6: 409–424.PubMedGoogle Scholar
  69. 69.
    McCabe M, Stablein D, Hawkins M. The modified group C experience-phase III randomized trials of IL-2 vs. IL-2/LAK in advanced renal cell carcinoma and advanced melanoma. Proc Am Soc Clin Oncol 1991; 10: 213.Google Scholar
  70. 70.
    Rosenberg SA, Lotze MT, Yang JC, et al. Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. [published erratum appears in J Natl Cancer Inst 1993 Jul 7; 85(13): 1091]. J Natl Cancer Inst 1993; 85: 622–632.PubMedGoogle Scholar
  71. 71.
    Spiess PJ, Yang JC, Rosenberg SA. In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2. J Natl Cancer Inst 1987; 79: 1067–1075.PubMedGoogle Scholar
  72. 72.
    Aebersold P, Hyatt C, Johnson S, et al. Lysis of autologous melanoma cells by tumor-infiltrating lymphocytes: association with clinical response. J Natl Cancer Inst 1991; 83: 932–937.PubMedGoogle Scholar
  73. 73.
    Hewitt HB, Blake ER, Walder AS. A critique of the evidence for active host defence against cancer, based on personal studies of 27 murine tumours of spontaneous origin. Br J Cancer 1976; 33: 241–259.PubMedGoogle Scholar
  74. 74.
    Chou T, Chang AE, Shu SY. Generation of therapeutic T lymphocytes from tumor-bearing mice by in vitro sensitization. Culture requirements and characterization of immunologic specificity. J Immunol 1988; 140: 2453–2461.PubMedGoogle Scholar
  75. 75.
    Shu SY, Chou T, Sakai K. Lymphocytes generated by in vivo priming and in vitro sensitization demonstrate therapeutic efficacy against a murine tumor that lacks apparent immunogenicity. J Immunol 1989; 143: 740–748.PubMedGoogle Scholar
  76. 76.
    Chang A, Yoshizawa H, Sakai K, et al. Clinical observations on adoptive immunotherapy with vaccine-primed T lymphocytes secondarily sensitized to tumor in vitro. Cancer Res 1993; 53: 1043–1050.Google Scholar
  77. 77.
    Van Wauwe JP, De Mey JR, Goossens JG. OKT3: a monoclonal anti-human T lymphocyte antibody with potent mitogenic properties. J Immunol 1980; 124: 2708–2713.PubMedGoogle Scholar
  78. 78.
    Kronenberg M, Siu G, Hood LE, Shastri N. The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Annu Rev Immunol 1986; 4: 529–591.PubMedGoogle Scholar
  79. 79.
    Clevers H, Alarcon B, Wileman T, Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol 1988; 6: 629–662.PubMedGoogle Scholar
  80. 80.
    Yoshizawa H, Sakai K, Chang A, et al. Specific adoptive immunotherapy mediated by tumor-draining lymph node cells sequentially activated with anti-CD3 and rIL-2. Jlmmunol 1991; 147: 729–737.Google Scholar
  81. 81.
    Yoshizawa H, Sakai K, Chang A, et al. Activation by anti-CD3 of tumor-draining lymph node cells for specific adoptive immunotherapy. Cell Immunol 1991; 134: 473–479.PubMedGoogle Scholar
  82. 82.
    Geiger JD, Wagner PD, Shu S, et al. A novel role for autologous tumour cell vaccination in the immunotherapy of the poorly immunogenic B16–BL6 melanoma. Surg Oncol 1992; 1: 199–208.PubMedGoogle Scholar
  83. 83.
    Chang A, Aruga A, Cameron M, et al. Adoptive immunotherapy with vaccine-primed lymph node cells secondarily activated with anti-CD3 and interleukin-2. J Clin Oncol 1997; 15: 796–807.PubMedGoogle Scholar
  84. 84.
    Leong SPL, Zhou YM, Peng M, et al. Adoptive immunotherapy of malignant melanoma using activated tumor draining lymph node T cells. Manuscript in preparation; 2001.Google Scholar
  85. 85.
    Shu S, Plautz G, Leong SPL. T-cell immunotherapy of melanoma and glioma. J Surg Oncol 2001; in press.Google Scholar
  86. 86.
    Gansbacher B, Zier K, Daniels B, et al. Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J Exp Med 1990; 172: 1217–1224.PubMedGoogle Scholar
  87. 87.
    Gansbacher B, Bannerji R, Daniels B, et al. Retroviral vector-mediated gamma-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity. Cancer Res 1990; 50: 7820–7825.PubMedGoogle Scholar
  88. 88.
    Asher AL, Mulâe JJ, Kasid A, et al. Murine tumor cells transduced with the gene for tumor necrosis factor-alpha. Evidence for paracrine immune effects of tumor necrosis factor against tumors. J Immunol 1991; 146: 3227–3234.PubMedGoogle Scholar
  89. 89.
    Tepper RI, Coffman RL, Leder P. An eosinophil-dependent mechanism for the antitumor effect of interleukin-4. Science 1992; 257: 548–551.PubMedGoogle Scholar
  90. 90.
    Dranoff G, Jaffee E, Lazenby A, et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 1993; 90: 3539–3543.PubMedGoogle Scholar
  91. 91.
    Restifo NP, Spiess Pi, Karp SE, et al. A nonimmunogenic sarcoma transduced with the cDNA for interferon gamma elicits CD8+ T cells against the wild-type tumor: correlation with antigen presentation capability. J Exp Med 1992; 175: 1423–1431.PubMedGoogle Scholar
  92. 92.
    Strome S, Chang A, Shu S, et al. Secretion of both IL-2 and IL-4 by tumor cells results in rejection and immunity. J. Immunother 1996; 19: 21–32.Google Scholar
  93. 93.
    Rosenberg SA, Aebersold P, Cornetta K, et al. Gene transfer into humans—immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction [see comments]. N Engl J Med 1990; 323: 570–578.PubMedGoogle Scholar
  94. 94.
    Grabbe S, Bruvers S, Gallo RL, et al. Tumor antigen presentation by murine epidermal cells. J Immunol 1991; 146: 3656–3661.PubMedGoogle Scholar
  95. 95.
    Shimizu J, Zou JP, Ikegame K, et al. Evidence for the functional binding in vivo of tumor rejection antigens to antigen-presenting cells in tumor-bearing hosts. J Immunol 1991; 146: 1708–1714.PubMedGoogle Scholar
  96. 96.
    Storkus WJ, Zeh HJd, Salter RD, et al. Identification of T-cell epitopes: rapid isolation of class I-presented peptides from viable cells by mild acid elution. J Immunother 1993; 14: 94–103.Google Scholar
  97. 97.
    Celluzzi CM, Mayordomo JI, Storkus WJ, et al. Peptide-pulsed dendritic cells induce antigen-specific CTL-mediated protective tumor immunity [see comments]. J Exp Med 1996; 183: 283–287.PubMedGoogle Scholar
  98. 98.
    Hu X, Chakraborty NG, Sporn JR, et al. Enhancement of cytolytic T lymphocyte precursor frequency in melanoma patients following immunization with the MAGE-1 peptide loaded antigen presenting cell-based vaccine. Cancer Res 1996; 56: 2479–2483.PubMedGoogle Scholar
  99. 99.
    Ribas A, Butterfield LH, McBride WH, et al. Genetic immunization for the melanoma antigen MART-1/Melan-A using recombinant adenovirus-transduced murine dendritic cells. Cancer Res 1997; 57: 2865–2869.PubMedGoogle Scholar
  100. 100.
    Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 1998; 392: 86–89.PubMedGoogle Scholar
  101. 101.
    Nouri-Shirazi M, Palucka KA, Chomarat P, et al. Dendritic cells phagocytose carcinoma-derived apoptotic bodies. J Leukoc Biol Suppl 1998; 2: 49.Google Scholar
  102. 102.
    Chang J, Peng M, Vaquerano J, et al. Induction of Th l response by dendritic cells pulsed with autologous melanoma apoptotic bodies. Anticancer Res 2001; 20: 1329–1336.Google Scholar
  103. 103.
    Rosenberg SA, Zhai Y, Yang JC, et al. Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp 100 melanoma antigens. J Natl Cancer Inst 1998; 90: 1894–1900.PubMedGoogle Scholar
  104. 104.
    Pieper R, Christian RE, Gonzales MI, et al. Biochemical identification of a mutated human melanoma antigen recognized by CD4(+) T cells [see comments]. J Exp Med 1999; 189: 757–766.PubMedGoogle Scholar

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© Humana Press Inc.,Totowa, NJ 2002

Authors and Affiliations

  • Stanley P. L. Leong
  • Suyu Shu

There are no affiliations available

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