T-cell-based immunotherapy of melanoma: what have we learned and how can we improve?

References

• Howe HL, Wingo PA, Thun MJ et al. Annual report to the nation on the status of cancer (1973 through 1998), featuring cancers with recent increasing trends. J. Nad Cancer Ind. 93,824-842 (2001).
   Google Scholar
• Zettersten E, Shaikh L, Ramirez R, Kashani-Sabet M. Prognostic factors in primary cutaneous melanoma. Surg Clin. North Am. 83,61–75 (2003).
   PubMed Web of Science ®Google Scholar
• Cooper JS. Radiation therapy of malignant melanoma. Dermatol Clin. 20,713–716 (2002).
   PubMed Web of Science ®Google Scholar
• Cascinelli N, Santinami M, Maurichi A, Patuzzo R, Pennacchioli E. World Health Organization experience in the treatment of melanoma. Surg. Clin. North Am. 83, 405–416 (2003).
   Google Scholar
• Soengas MS, Lowe SW. Apoptosis and melanoma chemoresistance. Oncogene 22, 3138–3151 (2003).
   PubMed Web of Science ®Google Scholar
• Guerry D. The cellular immunobiology of melanoma. In: Cutaneous oncology: pathophysiology, diagnosis and management. Miller SJ, Maloney ME (Eds). Blackwell Science, MA, USA 211–217 (1998).
   Google Scholar
• Stevanovic S. Identification of tumour-associated T-cell epitopes for vaccine development. Nature Rev. Cancer 2, 514–520 (2002).
   PubMed Web of Science ®Google Scholar
• •Discusses different approaches to identify tumor antigen epitopes and to improve their efficacy as an anticancer treatment.
   Google Scholar
• Ribas A, Butterfield LH, Glaspy JA, Economou JS. Current developments in cancer vaccines and cellular immunotherapy. J. Clin. OncoL 21,2415–2432(2003).
   PubMed Web of Science ®Google Scholar
• •Reviews the immunological basis of clinical trials that determine tumor antigen recognition and immune activation.
   Google Scholar
• Trikha M, Yan L, Nakada MT Monoclonal antibodies as therapeutics in oncology. Curr. Opin. Biotechnol 13,609–614 (2002).
   PubMed Web of Science ®Google Scholar
• Castelli C, Rivoltini L, Andreola G et al. T-cell recognition of melanoma-associated antigens.' Cell. Physiol 182,323–331 (2000).
   PubMed Web of Science ®Google Scholar
• Naftzger C, Takechi Y, Kohda H et al. Immune response to a differentiation antigen induced by altered antigen: a study of tumor rejection and autoimmunity. Proc. Nad Acad Sci. USA 93,14809–14814 (1996).
   PubMed Web of Science ®Google Scholar
• Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat. Immunol 3,611-618(2002).
   Google Scholar
• Parmiani G, Castelli C, Dalerba P et al. Cancer immunotherapy with peptide-based vaccines: what have we achieved? Where are we going?" Nad Cancer Ind. 94,805-818 (2002).
   Google Scholar
• ••Discusses the history of peptide-based vaccination strategies, methods to improve their immunogenicity and results of peptide-based clinical trials implemented to date.
   Google Scholar
• Milstein C, Waldmann H. Optimism after much pessimism: what next? Curr. Opin. Immunol 11, 589–591 (1999)•.
   Google Scholar
• Restifo NP, Wunderlich JR. Principles of tumor immunity: biology of cellular immune responses. In: Biologic Therapy of Cancer DeVita VT, Hellman S, Rosenberg SA (Eds). Lippincott Co., PA, USA 3-21(1996).
   Google Scholar
• •Summarizes the evidence for the notion that T-cells play a major role in tumor growth control.
   Google Scholar
• 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. Nat. Med. 4, 321–327 (1998).
   PubMed Web of Science ®Google Scholar
• Scheibenbogen C, Schmittel A, Keilholz U et al. Phase II trial of vaccination with tyrosinase peptides and granulocyte-macrophage colony stimulating factor in patients with metastatic melanoma. J. Immunother. 23,275–281 (2000).
   PubMed Web of Science ®Google Scholar
• Houghton AN, Mintzer D, Cordon-Cardo C et al Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: a Phase I trial in patients with malignant melanoma. Proc. Nad Acad. Sci. USA 82,1242–1126 (1985).
   Google Scholar
• Mittelman A, Chen ZJ, Kageshita T et al. Active specific immunotherapy in patients with melanoma. A clinical trial with mouse anti-idiotypic monoclonal antibodies elicited with syngeneic anti-high-molecular-weight-melanoma-associated antigen monoclonal antibodies. J. Clin. Invest. 86,2136–2144 (1990).
   Google Scholar
• Kawakami Y, Rosenberg SA. Immunobiology of human melanoma antigens MART-1 and gp100 and their use for immunogene therapy. Int. Rev. Immunol 14, 173–192 (1997).
   Google Scholar
• Rammensee HG, Weinschenk T, Gouttefangeas C, Stevanovic S. Towards patient-specific tumor antigen selection for vaccination. Immunol Rev. 188,164–176 (2002).
   PubMed Web of Science ®Google Scholar
• •Discusses the methodology for molecular analysis of the antigens expressed in a given tumor and identification of HLA class I antigen binding peptides from these antigens.
   Google Scholar
• Cox AL, Skipper J, Chen Yet al. Identification of a peptide recognized by five melanoma-specific human cytotcndc T- cell lines. Science 264,716–719 (1994).
   Google Scholar
• Old LJ, Chen YT. New paths in humancancer serology. J. Exp. Med. 187, 1163–1167 (1998).
   PubMed Web of Science ®Google Scholar
• Gilboa E. The makings of a tumor rejection antigen. Immunity 11,263–270(1999).
   PubMed Web of Science ®Google Scholar
• ••Discusses the characteristics of tumorantigens that make them appropriate tumor rejection antigens.
   Google Scholar
• Baurain JF, Colau D, van Baren N et al. High frequency of autologous antimelanoma CTL directed against an antigen generated by a point mutation in a new helicase gene. J. Immunol 164, 6057–6066 (2000).
   Google Scholar
• Marincola FM, Jaffee EM, Hicklin DJ, Ferrone S. Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv. immune/. 74, 181–273 (2000).
   PubMedGoogle Scholar
• •• Discusses the multiple mechanisms by which tumors escape immune recognition including HLA class I antigen, antigen processing machinery and tumor antigen loss.
   Google Scholar
• Yewdell J. Generating peptide ligands for MHC class I molecules. Mal Immunol 39 (2002).
   Web of Science ®Google Scholar
• •Dedicated to reviewing the molecular mechanisms behind the generation of HLA class I antigen-binding peptides, their presentation by HLA class I antigens and recognition of HLA class I antigen-peptide complexes by T-cells.
   Google Scholar
• Heath WR, Carbone FR Cross-presentation, dendritic cells, tolerance and immunity. Ann. Rev. Immund 19, 47–64 (2001).
   PubMed Web of Science ®Google Scholar
• •This in-depth review explores the biology behind cross-presentation.
   Google Scholar
• Li Z, Menoret A, Srivastava P. Roles of heat-shock proteins in antigen presentation and cross-presentation. Curr. Opin. Immunol 14, 45–51 (2002).
   Google Scholar
• •Focuses on the role HSPs play in chaperoning antigenic peptides and antigen presentation.
   Google Scholar
• Thery C, Amigorena S. The cell biology of antigen presentation in dendritic cells. Curr. Opin. Immunol 13, 45–51 (2001).
   PubMed Web of Science ®Google Scholar
• •Reviews the molecular mechanisms responsible for the control of DC antigen uptake and processing, for the generation of MHC—peptide complexes and for their transport to the cell surface.
   Google Scholar
• Barry M, Bleackley RC. Cytotcndc T- lymphocytes: all roads lead to death. Nat. Rev. Immunol 2,401–409 (2002).
   PubMed Web of Science ®Google Scholar
• •Discusses the mechanisms that are used by CTLs to destroy target cells.
   Google Scholar
• Darrow TL, Slingluff CL Jr, Seigler HF. The role of HLA class I antigens in recognition of melanoma cells by tumor-specific cytotcndc T-lymphocytes: evidence for shared tumor antigens. J. Immunol 142, 3329–3335 (1989).
   PubMed Web of Science ®Google Scholar
• Bystryn JC, Zeleniuch-Jacquotte A, Oratz R et al. Double-blind trial of a polyvalent, shed-antigen, melanoma vaccine. Clin. Cancer Res. 7, 1882–1887 (2001).
   PubMed Web of Science ®Google Scholar
• •Demonstrates that the median time to disease progression was 2.5 times longer in patients immunized with a polyvalent, shed-antigen melanoma vaccine.
   Google Scholar
• Berd D. MVaxTM: an autologous, hapten-modified vaccine for human cancer. Expert Opin. Biol. Ther. 2,335–342 (2002).
   PubMed Web of Science ®Google Scholar
• •Demonstrates an association between induction of DTH to unmodified autologous tumor cells and survival in stage III and stage IV patients immunized with an autologous tumor cell vaccine conjugated to the hapten dinitrophenyl and mixed with BCG (M-VaxTm).
   Google Scholar
• DiFronzo LA, Gupta RK, Essner R et al. Enhanced humoral immune response correlates with improved disease-free and overall survival in American Joint Committee on Cancer stage II melanoma patients receiving adjuvant polyvalent vaccine. J. Clin. Oncol 20,3242–3248 (2002).
   PubMed Web of Science ®Google Scholar
• •Demonstrates an association between antibody titers and survival in patients immunized with an allogeneic whole-cell vaccine.
   Google Scholar
• Ward S, Casey D, Labarthe MC et al. Immunotherapeutic potential of whole tumour cells. Cancer Immunol Immunother. 51, 351–357 (2002).
   PubMed Web of Science ®Google Scholar
• •Demonstrates the advantages of using whole tumor cell vaccine preparations and the possible mechanisms by which they stimulate an immune response.
   Google Scholar
• Mahvi DM, Shi FS, Yang NS et al. Immunization by particle-mediated transfer of the granulocyte-macrophage colony-stimulating factor gene into autologous tumor cells in melanoma or sarcoma patients: report of a Phase I/IB study. Hum. Gene Ther 13, 1711–1721 (2002).
   PubMed Web of Science ®Google Scholar
• Parmiani G, Arienti F, Melani C et al. Gene therapy of melanoma. In: Melanoma, Techniques and Protocols. Nickoloff BJ (Ed.) Humana Press, NJ, USA 203–222 (2002).
   Google Scholar
• Soiffer R, Hodi FS, Haluska F et al. Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma. J. Clin. Oncol 21,3343–3350 (2003).
   PubMed Web of Science ®Google Scholar
• Parkhurst MR, DePan C, Riley JP, Rosenberg SA, Shu S. Hybrids of dendritic cells and tumor cells generated by electrofusion simultaneously present immunodominant epitopes from multiple human tumor- associated antigens in the context of MHC class I and class II molecules.' Immund 170, 5317–5325 (2003).
   Google Scholar
• Krause SW, Neumann C, Soruri A et al. The treatment of patients with disseminated malignant melanoma by vaccination with autologous cell hybrids of tumor cells and dendritic cells. J. Immunother. 25,421–428 (2002).
   PubMed Web of Science ®Google Scholar
• •Demonstrates that hybrid DC tumor cell vaccines can be safely applied, however clinical efficacy is marginal.
   Google Scholar
• Srivastava P. Interaction of heat shock proteins with peptides and antigen-presenting cells: chaperoning of the innate and adaptive immune responses. Ann. Rev. Immunol 20,395–425 (2002).
   PubMed Web of Science ®Google Scholar
• •Reviews all aspects of HSP biology and is an excellent starting point for those interested in HSPs.
   Google Scholar
• Theobald M, Ruppert T, Kuckelkorn U et al. The sequence alteration associated with a mutational hotspot in p53 protects cells from lysis by cytotoxic T-lymphocytes specific for a flanking peptide epitope. J. Exp. Med. 188,1017-1028 (1998).
   Google Scholar
• Morel S, Levy F, Burlet-Schiltz 0 et al. Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells. Immunity 12,107–117 (2000).
   Google Scholar
• •First study to demonstrate upregulation of components of the immunoproteasome components results in the loss of MA-derived peptide epitopes.
   Google Scholar
• Sun Y, Sijts AJ, Song M et al. Expression of the proteasome activator PA28 rescues the presentation of a cytotoxic T-lymphocyte epitope on melanoma cells. Cancer Res. 62, 2875–2882 (2002).
   PubMed Web of Science ®Google Scholar
• •First study to demonstrate defects in immunoproteasome activator PA28 expression results in the loss of MA-derived peptide epitopes.
   Google Scholar
• Aichele P, Brduscha-Riem K, Zinkernagel RM, Hengartner H, Pircher H. T-cell priming versus T-cell tolerance induced by synthetic peptides. J. Exp. Med. 182, 261–266 (1995).
   PubMed Web of Science ®Google Scholar
• •Demonstrates that immunization with synthetic peptides can induce both T cell tolerance and T cell priming depending on route and frequency of immunization.
   Google Scholar
• Toes RE, Blom RJ, Offringa R, Kast WM, Melief CJ. Enhanced tumor outgrowth after peptide vaccination. Functional deletion of tumor-specific CTL induced by peptide vaccination can lead to the inability to reject tumors. J. Immunol 156, 3911–3918 (1996).
   Google Scholar
• De Visser KE, Schumacher TN, Kruisbeek AM. CD8. T-cell tolerance and cancer immunotherapy. J. Immunother. 26,1-11 (2003).
   Google Scholar
• •Discusses the fate and functional capacities of self-specific T-cells with specificity for tissue-restricted self-antigens and for ubiquitously expressed self-antigens.
   Google Scholar
• Rosenberg SA, Zhai Y, Yang JC et al. Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens. J. Nad Cancer Inst. 90, 1894–1900 (1998).
   Google Scholar
• Coulie PG, Karanikas V, Lurquin C et al. Cytolytic T-cell responses of cancer patients vaccinated with a MAGE antigen. Immunol Rev. 188,33–42 (2002).
   PubMed Web of Science ®Google Scholar
• Sun Y, Schadendorf D. Gene-based immunotherapy of skin cancers. Recent Results Cancer Res. 160,170–184 (2002).
   PubMedGoogle Scholar
• Pardoll DM, Beckerleg AM. Exposing the immunology of naked DNA vaccines. Immunity 3, 165–169 (1995).
   PubMed Web of Science ®Google Scholar
• •Discusses the mechanisms by which DNA can stimulate an immune response.
   Google Scholar
• Gabrilovich DI. Dendritic cell vaccines for cancer treatment. Curr. Opin. Mal Then: 4, 452–458 (2002).
   Google Scholar
• Engleman EG. Dendritic cell-based cancer immunotherapy. Semin. Oncol 3\(Suppl. 8), 23–29 (2003).
   Google Scholar
• •Discusses the use of DCs in immunotherapy and some of the clinical trials that have been conducted.
   Google Scholar
• Moudgil KD, Sercarz EE. The self-directed T-cell repertoire: its creation and activation. Rev. Immunogenet. 2,26–37 (2000).
   PubMedGoogle Scholar
• Mason D. Some quantitative aspects of T- cell repertoire selection: the requirement for regulatory T-cells. Immunol Rev. 182, 80–88 (2001).
   PubMed Web of Science ®Google Scholar
• Parkhurst MR, Salgaller ML, Southwood S et al. Improved induction of melanoma-reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0201-binding residues. J. Immund 157, 2539–2548 (1996).
   Google Scholar
• •Demonstrates that modified gp100 peptides may be more immunogenic than the native epitopes.
   Google Scholar
• Rivoltini L, Squarcina P, Loftus DJ et al. A superagonist variant of peptide MART1/Melan A27-35 elicits antimelanoma CD8. T-cells with enhanced functional characteristics: implication for more effective immunotherapy. Cancer Res. 59,301-306 (1999).
   Google Scholar
• Naftzger C, Takechi Y, Kohda H et al. Immune response to a differentiation antigen induced by altered antigen: a study of tumor rejection and autoimmunity. Proc. Nad Acad. Sci. USA 93,14809–14814 (1996).
   PubMed Web of Science ®Google Scholar
• •Demonstrates that tolerance to self-MA can be broken by immunization with altered MA (e.g., homologous xenogeneic protein or protein expressed in insect cells) in a syngeneic murine melanoma model.
   Google Scholar
• Steitz J, Bruck J, Steinbrink K et al. Genetic immunization of mice with human tyrosinase-related protein 2, implications for the immunotherapy of melanoma. Int. J. Cancer 86,89–94 (2000).
   Google Scholar
• Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T-cell responses: mechanisms and manipulation in tumor immunotherapy. Ann. Rev. Immunol 19, 565–594 (2001).
   Google Scholar
• •Provides an excellent description of the cellular and molecular mechanisms of immune response regulation by CTLA-4 and its manipulation as a strategy for tumor immunotherapy.
   Google Scholar
• Phan GQ, Yang JC, Sherry RM et al. Cancer regression and autoimmunity induced by cytotoxic T-Iymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc. Nad Acad. Sci. USA 100,8372–8377 (2003).
   Google Scholar
• Schreiber S, Kampgen E, Wagner E et al. Immunotherapy of metastatic malignant melanoma by a vaccine consisting of autologous interleukin-2-transfected cancer cells: outcome of a Phase I study. Hum. Gene Then: 10,983-993 (1999).
   Google Scholar
• Jager E, Maeurer M, Hohn H et al. Clonal expansion of Melan A-specific cytotoxic T-lymphocytes in a melanoma patient responding to continued immunization with melanoma-associated peptides. Int. J. Cancer 86,538–547 (2000).
   PubMed Web of Science ®Google Scholar
• Clay TM, Hobeika AC, Mosca PJ, Lyerly HK, Morse MA. Assays for monitoring cellular immune responses to active immunotherapy of cancer. Clin. Cancer Res. 7, 1127–1135 (2001).
   PubMed Web of Science ®Google Scholar
• •Provides an in-depth review of the assays utilized to monitor immune responses in patients treated with active specific immunotherapy.
   Google Scholar
• Thurner B, Haendle I, Roder C et al. Vaccination with Mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T-cells and induces regression of some metastases in advanced stage IV melanoma. J. Exp. Med. 190,1669-1678 (1999).
   Google Scholar
• Morse MA, Deng Y, Coleman D et at. A Phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen. Clin. Cancer Res. 5,1331-1338 (1999).
   Google Scholar
• McNeel DG, Schiffman K, Disis ML. Immunization with recombinant human granulocyte-macrophage colony-stimulating factor as a vaccine adjuvant elicits both a cellular and humoral response to recombinant human granulocyte-macrophage colony-stimulating factor. Blood 93,2653–2659 (1999).
   Google Scholar
• Jager D, Jager E, Knuth A. Immune responses to tumour antigens: implications for antigen specific immunotherapy of cancer.' Clin. Pathol. 54,669-674 (2001).
   Google Scholar
• Cormier JN, Salgaller ML, Prevette T et al. Enhancement of cellular immunity in melanoma patients immunized with a peptide from MART-1/Melan A. Cancer' Sci. Am. 3,37-44 (1997).
   Google Scholar
• Schmittel A, Keilholz U, Scheibenbogen C. Evaluation of the interferon-y ELISpot-assay for quantification of peptide specific T-lymphocytes from peripheral blood. J. Immunol. Methods 210,167–174 (1997).
   Google Scholar
• •Highlighting the utility of the ELISpot assays, this article demonstrates that the frequency of peptide specific CDS T-cells can be reliably determined from peripheral blood with the IFN-y ELISpot assay.
   Google Scholar
• Lee PP, Yee C, Savage PA et al. Characterization of circulating T-cells specific for tumor-associated antigens in melanoma patients. Nat. Med. 5,677–685 (1999).
   PubMed Web of Science ®Google Scholar
• Manne J, Mastrangelo MJ, Sato T, Berd D. TCR rearrangement in lymphocytes infiltrating melanoma metastases after administration of autologous dinitrophenyl-modified vaccine. J. Immunol. 169,3407–3412 (2002).
   PubMed Web of Science ®Google Scholar
• Reynolds SR, Zeleniuch-Jacquotte A, Shapiro RL et aL Vaccine-induced CD8* T-cell responses to MAGE-3 correlate with clinical outcome in patients with melanoma. Clin. Cancer Res. 9,657-662(2003).
   Google Scholar
• •Demonstrates an increase in the frequency of MAGE-3-specific T-cells after vaccination with a polyvalent, shed-antigen melanoma vaccine.
   Google Scholar
• Morton DL, Hsueh EC, Essner R et al. Prolonged survival of patients receiving active immunotherapy with Canywdn therapeutic polyvalent vaccine after complete resection of melanoma metastatic to regional lymph nodes. Ann. Surg 236, 438–448 (2002).
   PubMed Web of Science ®Google Scholar
• •Demonstrates that a patient's pretreatment tumor burden is of critical importance for generation of a tumor-specific immune response.
   Google Scholar
• Sondak VK, Liu PY, Tuthill et al. Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: overall results of a randomized trial of the Southwest Oncology Group. J. Clin. Oncol. 20, 2058–66 (2002).
   PubMed Web of Science ®Google Scholar
• Sosman JA, Unger JM, Liu PY et al. Southwest Oncology Group. Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: impact of HLA class I antigen expression on outcome. J. Clin. OncoL 20,2067-2075 (2002).
   Google Scholar
• Belli F, Testori A, Rivoltini L et al. Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings.' Clin. OncoL 20, 4169–4180 (2002).
   Google Scholar
• •Demonstrates that vaccination of melanoma patients with autologous HSP gp96 is feasible, devoid of significant toxicity and is capable of inducing clinical and tumor-specific T-cell responses in patients.
   Google Scholar
• Rivoltini L, Castelli C, Carrabba M et al. Human tumor-derived heat shock protein 96 mediates in vitro activation and in vivo expansion of melanoma and colon carcinoma-specific T-cells. J. ImmunoL171, 3467–3474 (2003).
   Google Scholar
• Jager E, Ringhoffer M, Dienes HP et al. Granulocyte-macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo. Int.j Cancer 67, 54–62 (1996).
   PubMed Web of Science ®Google Scholar
• Marchand M, van Baren N, Weynants P et al. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-Al. Inf. J. Cancer 80,219–230 (1999).
   Google Scholar
• •Demonstrates clinical responses in melanoma patients vaccinated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-Al in spite of the lack of detectable tumor-specific T-cell immunity in the immunized patients.
   Google Scholar
• Restifo NP, Sznol M, Schwarz SL et al. Impact of cytokine administration on the generation of antitumor reactivity in patients with metastatic melanoma receiving a peptide vaccine. J. Immunol. 163,1690–1695 (1999).
   PubMed Web of Science ®Google Scholar
• Wang F, Bade E, Kuniyoshi C et al. Phase I trial of a MART-1 peptide vaccine with incomplete Freund's adjuvant for resected high-risk melanoma. Clin. Cancer Res. 5, 2756–2765 (1999).
   Google Scholar
• Weber JS, Hua FL, Spears L et al. A Phase I trial of an HLA-Al-restricted MAGE-3 epitope peptide with IFA in patients with resected high-risk melanoma. J. Immunother 5,431–440 (1999).
   Google Scholar
• Jager E, Gnjatic S, Nagata Yet al. Induction of primary NY-ESO-1 immunity, CD8. T-lymphocyte and antibody responses in peptide-vaccinated patients with NY-ES0-1. cancers. Proc. Nad Acad Sci. USA 97, 12198–12203 (2000).
   Google Scholar
• Lewis JJ, Janetzki S, Schaed S et al. Evaluation of CD8. T-cell frequencies by the ELIspot assay in healthy individuals and in patients with metastatic melanoma immunized with tyrosinase peptide. Int. J. Cancer 87,391–398 (2000).
   Google Scholar
• Lee P, Wang F, Kuniyoshi J et al. Effects of interleukin-12 on the immune response to a multipeptide vaccine for resected metastatic melanoma. J. Clin. OncoL 19, 3836–3847 (2001).
   Google Scholar
• Slingluff CL Jr, Yamshchikov G, Neese P et al. Phase I trial of a melanoma vaccine with gp100 (280–288) peptide and tetanus helper peptide in adjuvant: immunologic and clinical outcomes. Clin. Cancer Res. 7, 3012–3024 (2001).
   Google Scholar
• Schaed SG, Klimek VM, Panageas KS et aL T- cell responses against tyrosinase 368-376(370D) peptide in HLA*A0201. melanoma patients: randomized trial comparing incomplete Freund's adjuvant, granulocyte-macrophage colony-stimulating factor and QS-21 as immunological adjuvants. Clin. Cancer Res. 8,967-972 (2002).
   Google Scholar
• Marchand M, Punt CJ, Aamdal S et al. Immunization of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2: a clinical report. Eur. J. Cancer 39,70–77 (2003).
   Google Scholar
• Scheibenbogen C, Schadendorf D, Bechrakis et al. Effects of granulocyte-macrophage colony-stimulating factor and foreign helper protein as immunologic adjuvants on the T-cell response to vaccination with tyrosinase peptides. Int. J. Cancer 104,188–194 (2003).
   PubMed Web of Science ®Google Scholar
• Smith JW II, Walker EB, Fox BA et al. Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8. T-cell responses. J. Clin. Oncol. 21, 1562–1573 (2003).
   Google Scholar
• Weber J, Sondak VK, Scotland R et al. Granulocyte-macrophage-colony-stimulating factor added to a multipeptide vaccine for resected Stage II melanoma. Cancer 97,186–200 (2003).
   PubMed Web of Science ®Google Scholar
• Kirkwood JM, Strawderman MH, Emstoff MS et aL Interferona-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Co-operative Oncology Group Trial Est 1684." Clin. Once/ 14, 7–17 (1996).
   Google Scholar
• Atkins MB, Lotze MT, Dutcher JP. High- dose recombinant interleukin-2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993." Clin. OncoL 17, 2105–2116 (1999).
   Google Scholar
• Lechner F, Wong DK, Dunbar PR et al. Analysis of successful immune responses in persons infected with hepatitis C virus. J. Exp. Med. 191, 1499–1512 (2000).
   PubMed Web of Science ®Google Scholar
• Lotze MT, Shurin M, Esche C et al. Interleukin-2: developing additional cytokine gene therapies using fibroblasts or dendritic cells to enhance tumor immunity Cancer Sci. Am. 6\(Suppl. 1), S61—S66 (2000).
   Google Scholar
• Mackensen A, Herbst B, Chen JL et al. Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34' hematopoietic progenitor cells. Int. J. Cancer 86, 385–392 (2000).
   Google Scholar
• Banchereau J, Palucka AK, Dhodapkar Met al. Immune and clinical responses in patients with metastatic melanoma to CD34' progenitor-derived dendritic cell vaccine. Cancer Res. 61,6451-6458 (2001).
   Google Scholar
• Gajewski TF, Fallarino F, Ashikari A, Sherman M. Immunization of HLA-A27 melanoma patients with MAGE-3 or MelanA peptide-pulsed autologous peripheral blood mononuclear cells plus recombinant human interleukin-12. Clin. Cancer Res. 7, S895—S901 (2001).
   Google Scholar
• Schadendorf D, Nestle FO. Autologous dendritic cells for treatment of advanced cancer — an update. Recent Results Cancer Res. 158, 236–248 (2001).
   PubMedGoogle Scholar
• Chang AE, Redman BG, Whitfield JR et al A Phase I trial of tumor lysate-pulsed dendritic cells in the treatment of advanced cancer. Clin. Cancer Res. 8, 1021–1032 (2002).
   PubMed Web of Science ®Google Scholar
• Rosenberg SA, Yannelli JR, Yang JC et al. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin-2. J. Natl Cancer Inst. 86, 1159–1166 (1994).
   Google Scholar
• Dudley ME, Wunderlich J, Nishimura MI et al. Adoptive transfer of cloned melanoma-reactive T-lymphocytes for the treatment of patients with metastatic melanoma.' inimunother 24, 363–373 (2001).
   PubMed Web of Science ®Google Scholar
• Dudley ME, Wunderlich JR, Yang JC 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. 25, 243–251 (2002).
   PubMed Web of Science ®Google Scholar
• Economou JS, Belldegrun AS, Glaspy J et al In vivo trafficking of adoptively transferred interleukin-2 expanded tumor-infiltrating lymphocytes and peripheral blood lymphocytes. Results of a double gene marking trial." Clin. Invest. 97, 515–521 (1996).
   Google Scholar
• Figlin RA, Thompson JA, Bukowski RM et al. Multicenter, randomized, Phase III trial of CD8 tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma. J. Clin. Oncol. 17, 2521–2529 (1999)•.
   Google Scholar
• Oelke M, Maus MV, Didiano D et al. a vivo induction and expansion of antigen-specific cytotmdc T-cells by HLA-Ig-coated artificial antigen-presenting cells. Nat. Med. 9, 619–624 (2003).
   PubMed Web of Science ®Google Scholar
• •Describes the techniques for reproducible expansion of disease-specific CTLs for clinical approaches to adoptive immunotherapy.
   Google Scholar
• Yee C, Thompson JA, Byrd D 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).
   Google Scholar
• Dudley ME, Wunderlich JR, Robbins PF et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298, 850–824 (2002).
   PubMed Web of Science ®Google Scholar
• Onyango P. Genomics and cancer. Curr. Opin. Oncol. 14, 79–85 (2002).
   PubMed Web of Science ®Google Scholar
• Ferrone S. Tumour immune escape. Semin. Cancer Biol. 12 (2002).
   Google Scholar
• •• Reviews the multiple mechanisms of immune escape utilized by tumor cells.
   Google Scholar
• Rivoltini L, Carrabba M, Huber Vet al. Immunity to cancer: attack and escape in T-lymphocyte-tumor cell interaction. Immunol. Rev. 188, 97–113 (2002).
   Google Scholar
• Finke J, Ferrone S, Frey A, Mufson A, Ochoa A. Where have all the T-cells gone? Mechanisms of immune evasion by tumors. Immunol. Today 20, 158–160 (1999).
   Google Scholar
• •Suggests that TCR C chain defects and lymphocyte apoptosis are manifestations of long-lasting negative effects of tumor on the immune system in head and neck cancer patients.
   Google Scholar
• Nielsen MB, Monsurro V, Migueles SA et al. Status of activation of circulating vaccine-elicited CD8. T-cells. J. Immunol. 165, 2287–2296 (2000).
   Google Scholar
• Panelli MC, Riker A, Kammula U et al. Expansion of tumor-T-cell pairs from fine needle aspirates of melanoma metastases. J. Immunol. 164, 495–504 (2000).
   PubMed Web of Science ®Google Scholar
• Kammula US, Lee KH, Riker A et a/. Functional analysis of antigen-specific T-lymphocytes by serial measurement of gene expression in peripheral blood mononuclear cells and tumor specimens. J. Immunol. 163, 6867–6875 (1999).
   Google Scholar
• Ivanov VN, Bhoumik A, Ronai Z. Death receptors and melanoma resistance to apoptosis. Oncogene 22, 3152–3161 (2003).
   Google Scholar
• Singh RK, Varney ML. IL-8 expression in malignant melanoma: implications in growth and metastasis. Hi std. Hi stopathol. 15, 843–849 (2000).
   Google Scholar
• Streit M, Detmar M. Angiogenesis, lymphangiogenesis and melanoma metastasis. Oncogene 22, 3172–3179 (2003).
   PubMed Web of Science ®Google Scholar
• Yu Z, Restifo NP. Cancer vaccines: progress reveals new complexities. J. Clin. Invest. 110, 289–294 (2002).
   PubMed Web of Science ®Google Scholar
• Chames P, Hufton SE, Coulie PG, Uchanska-Ziegler B, Hoogenboom HR. Direct selection of a human antibody fragment directed against the tumor T-cell epitope HLA-Al-MAGE-Al from a nonimmunized phage-Fab library. Proc. Natl Acad Sci. USA 97, 7969–7974 (2000).
   Google Scholar
• •Describes the successful isolation of human Fab fragments, which recognize a specific HLA-A1-MAGE1 peptide complex.
   Google Scholar
• Denkberg G, Cohen CJ, Lev A et a/. Direct visualization of distinct T-cell epitopes derived from a melanoma tumor-associated antigen by using human recombinant antibodies with MHC-restricted T-cell receptor-like specificity. Proc. Natl Acad Sci. USA 99, 9421–9426 (2002).
   Google Scholar
• Lev A, Denkberg G, Cohen CJ et al. Isolation and characterization of human recombinant antibodies endowed with the antigen-specific, major histocompatibility complex-restricted specificity of T-cells directed toward the widely expressed tumor T-cell epitopes of the telomerase catalytic subunit. Cancer Res. 62, 3184–3194 (2002).
   PubMed Web of Science ®Google Scholar