Abstract
Vaccination against tumors promises selective destruction of malignant cells by the host’s immune system. Molecular cancer vaccines rely on recently identified tumor antigens as immunogens. Tumor antigens can be applied in many forms, as genes in recombinant vectors, as proteins or peptides representing T cell epitopes.
Analysis of various aspects indicates some advantage for peptide-based vaccines over the other modalities. Further refinements and extensively monitored clinical trials are necessary to advance molecular cancer vaccines from concepts into powerful therapy.
Similar content being viewed by others
Abbreviations
- CTL:
-
cytotoxic T lymphocyte
- TA:
-
tumor antigen
- TCR:
-
T cell receptor
- TIL:
-
tumor infiltrating lymphocyte
References
Ahlers JD, Dunlop N, Ailing DW et al: Cytokine-in-adjuvant steering of the immune response phenotype to HIV-1 vaccine constructs: granulocyte-macrophage colony-stimulating factor and TNF-alpha synergize with IL-12 to enhance induction of cytotoxic T lymphocytes. J Immunol 158:3947–3958, 1997.
Allsopp CEM, Plebanski M, Gilbert S et al: Comparison of numerous delivery systems for the induction of cytotoxic T lymphocytes by immunization. Eur J Immunol 26:1951–1959, 1996.
Altman JD, Moss PAH, Goulder PJR et al: Phenotypic analysis of antigen-specific T lymphocytes. Science. 274:94–96, 1996.
Anichini A, Mortarini R, Maccalli C et al: Cytotoxic T cells directed to tumor antigens not expressed on normal melanocytes dominate HLA-A2.1-restricted immune repertoire to melanoma. J Immunol 156: 208–217, 1996.
Arienti F, Sule-Suso J, Belli F et al: Limited antitumor T cell response in melanoma patients vaccinated with interleukin-2 gene-transduced allogeneic melanoma cells. Hum Gene Ther 7:1955–1963, 1996.
Barth A, Hoon DS, Foshag LJ et al: Polyvalent melanoma cell vaccine induces delayed-type hypersensitivity and in vitro cellular immune response. Cancer Res 54:3342–3345, 1994.
Bloom MB, Lalley-Perry D, Robbins PE et al: Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma. J Exp Med 185:453–459, 1997.
Boon T and van der Bruggen P: Human tumor antigens recognized by T lymphocytes. J Exp Med 183:725–729, 1996.
Boon T, Van Snick J, Van Pel A et al: Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. II. T lymphocyte-mediated cytolysis. J Exp Med 152:1184–1193, 1980.
Bosch GJ, Joosten AM, Kessler JH et al: Recognition of BCR-ABL positive leukemic blasts by human CD4+ T cells elicited by primary in vitro immunization with a BCR-ABL breakpoint peptide. Blood 88:3522–3527, 1996.
Brass N, Heckel D, Sahin U et al: Translation initiation factor eIF-4gamma is encoded by an amplified gene and induces an 173 immune response in squamous cell lung carcinoma. Hum Mol Genet 6:33–39, 1997.
Brändie D, Brasseur F, Weynants P et al: A mutated HLA-A2 Molecule recognized by autologous cytotoxic T lymphocytes on a human renal cell carcinoma. J Exp Med 183:2501–2508, 1996.
Bremers AJ, van der Burg SH, Kuppen PJ et al: The use of Epstein-Barr virus-transformed B lymphocyte cell lines in a peptide-reconstitution assay: identification of CEA-related HLA-A*0301-restricted potential cytotoxic T-lymphocyte epitopes. J Immunother Emphasis Tumor Immunol. 18:77–85, 1995.
Brusic V, Rudy G, Kyne AP et al: MHCPEP: a database of MHC-binding peptides. Nucleic Acids Res 24:242–244, 1996.
Buschle M, Schmidt W, Zauner W et al: Transloading of tumor antigen-derived peptides into antigen-presenting cells. Proc Natl Acad Sci USA 94:3256–3261, 1997.
Bystryn JC, Rigel D, Friedman RJ et al: Prognostic significance of hypopigmentation in malignant melanoma. Arch Dermatol 123:1053–1055, 1987.
Celts E, Tsai V, Crimi C et al: Induction of anti-tumor cytotoxic T lymphocytes in normal humans using primary cultures and synthetic peptide epitopes. Proc Natl Acad Sci USA. 91:2105–2109, 1994.
Chen PW, Wang M, Bronte Vet al: Therapeutic antitumor response after immunization with a recombinant adenovirus encoding a model tumor-associated antigen. J Immunol 156:224–231, 1996.
Chen YT, Scanlan MJ, Sahin U et al: A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA 94:1914–1918, 1997.
Chen YT, Stochert E, Jungbluth A et al: Serological analysis of Melan-A(MART-l), a melanocyte-specific protein homogeneously expressed in human melanomas. Proc Natl Acad Sci USA 93:5915–5919, 1996.
Coulie PG, Lehmann F, Lethe B et al: A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma. Proc Natl Acad Sci USA 92:7976–7980, 1995.
Cox AL, Skipper J, Chen Y et al: Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines. Science 264:716–718, 1994.
de Bergeyck V, De Plaen E, Chomez P et al: An intracisternal A-particle sequence codes for an antigen recognized by syngeneic cytolytic T lymphocytes on a mouse spontaneous leukemia. Eur J Immunol 24:2203–2212, 1994.
De Plaen E, Lurquin C, Van Pel A et al: Immunogenic (tum-) variants of mouse tumor P815: cloning of the gene of turn-antigen P91A and identification of the turn-mutation. Proc Natl Acad Sci USA 85:2274–2278, 1988.
del Guercio MF, Sidney J, Hermanson G et al: Binding of a peptide antigen to multiple HLA alleles allows definition of an A2-like supertype. J Immunol 154:685–693, 1995.
Deres K, Schild H, Wiesmuller KH et al: In vivo priming of virus-specific cytotoxic T lymphocytes with synthetic lipopeptide vaccine. Nature 342:561–564, 1989.
DiBrino M, Tsuchida T, Turner RV et al: HLA-A1 and HLA-A3 T cell epitopes derived from influenza virus proteins predicted from peptide binding motifs. J Immunol 151:5930–5935, 1993.
Disis ML, Gralow JR, Bernhard H et al: Peptide-based, but not whole protein, vaccines elicit immunity to HER-2/neu, an oncogenic self-protein. J Immunol 156:3151–3158, 1996.
Domenech N, Henderson RA, and Finn OJ; Identification of an HLA-A11-restricted epitope from the tandem repeat domain of the epithelial tumor antigen mucin. J Immunol 155:4766–4774, 1995.
Donnelly JJ, Friedman A, Martinez D et al: Preclinical efficacy of a prototype DNA vaccine: enhanced protection against antigenic drift in influenza virus. Nature Med 1:583–587, 1995.
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 90:3539–3543, 1993.
Dranoff G and Mulligan RC: Gene transfer as cancer therapy. Adv Immunol 58:417–454, 1995.
Dudley ME and Roopenian DC: Loss of a unique tumor antigen by cytotoxic T lymphocyte immunoselection from a 3-Methylcholanthrene-induced mouse sarcoma reveals secondary unique and shared antigens. J Exp Med 184:441–447, 1996.
Engelhard VH: Structure of peptides associated with class I and class II MHC molecules. Annu Rev Immunol 12:181–207, 1994.
Falk K, Rotzschke O, Stevanovic S et al: Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351:290–296, 1991.
Fearon ER, Pardoll DM, Itaya T et al: Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 60:397–403, 1990.
Feltkamp MC, Vreugdenhil GR, Vierboom MP et al: Cytotoxic T lymphocytes raised against a subdominant epitope offered as a synthetic peptide eradicate human papillomavirus type 16-induced tumors. Eur J Immunol 25:2638–2642, 1995.
Fisk B, Anderson BW, Gravitt KR et al: Identification of naturally processed human ovarian peptides recognized by tumor-associated CD8+ cytotoxic T lymphocytes. Cancer Res 57:87–93, 1997.
Fleischhauer K, Fruci D, van Endert PM et al: Characterisation of antigenic peptides presented by HLA-B44 molecules on tumor cells expressing the gene MAGE-3. Int J Cancer 68:622–628, 1996.
Fu TM, Ulmer JB, Caulfield MJ et al: Priming of cytotoxic T lymphocytes by DNA vaccines: requirement for professional antigen presenting cells and evidence for antigen transfer from myocytes. Mol Med 3:362–371, 1997.
Gaugler B, Brouwenstijn N, Vantomme V et al: A new gene coding for an antigen recognized by autologous cytolytic T lym-phocytes on a human renal carcinoma. Immunogenetics 44:323–330, 1996.
Gaugler B, van den Eynde B, van der Bruggen P et al: Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes. J Exp Med 179:921–930, 1994.
Gilloux Y, Lucas S, Brichard VG et al: A peptide recognized by human cytolytic T lymphocytes on HLA-A2 melanomas is encoded by an intron sequence of the N-acteylglucosaminyl-transferase V gene. J Exp Med 183:1173–1183, 1996.
Gjertsen MK, Bakka A, Breivik J et al: Vaccination with mutant ras peptides and induction of T-cell responsiveness in pancreatic carcinoma patients carrying the corresponding RAS mutation. Lancet 346:1399–1400, 1995.
Grey HM, Ruppert J, Vitiello A et al: Class I MHC-peptide interactions: structural requirements and functional implications. Cancer Surv 22:37–49: 37-49, 1995.
Grohmann U, Bianchi R, Ayroldi E et al: A tumor-associated and self antigen peptide presented by dendritic cells may induce T cell anergy in vivo, but IL-12 can prevent or revert the anergic state. J Immunol 158:3593–3602, 1997.
Hahne M, Rimoldi D, Schroeter M et al: Melanoma cell expression of Fas(Apo-l/CD95) ligand: implication for tumor immune escape. Science 274:1363–1366, 1996.
Hakomori SI: Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens. Adv Cancer Res 52:257–331, 1989.
Hara I, Takechi Y and Houghton AN: Implicating a role for immune recognition of self in tumor rejection: passive immunization against the brown locus protein. J Exp Med 182:1609–1614, 1995.
Hayashi H, Matsubara H, Yokota T et al: Molecular cloning and characterization of the gene encoding mouse melanoma antigen by cDNA library transfection. J Immunol 149:1223–1229, 1992.
Heike M, Schlaak J, Schulze-Bergkamen H et al: Specificities and functions of CD4+ HLA class II-restricted T cell clones against a human sarcoma. J Immunol 156:2205–2213, 1996.
Herman J, van der Bruggen P, Luescher IF et al: A peptide encoded by the human MAGE3 gene and presented by HLA-B44 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE3. Immunogenetics 43:377–383, 1996.
Herr W, Schneider J, Lohse AW et al: Detection and quantification of blood-derived CD8+ T lymphocytes secreting tumor necrosis factor alpha in response to HLA-A2.1-binding melanoma and viral peptide antigens. J Immunol Methods 191:131–142, 1996.
Hoshino T, Seki N, Kikuchi M et al: HLA class-I-restricted and tumor-specific CTL in tumor-infiltrating lymphocytes of patients with gastric cancer. Int J Cancer 70:631–638, 1997.
Huang AYC, Golumbek P, Ahmadzadeh M et al: Role of bone marrow-derived cells in presenting MHC class-I restricted tumor antigens. Science 264:961–965, 1994.
Huang AYC, Gulden PH, Woods AS et al: The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product. Proc Natl Acad Sci USA 93:9730–9735, 1996.
Ikeda H, Lethe B, Lehmann F et al: Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity 6:197–208, 1997.
Irvine KR, Rao JB, Rosenberg SA et al: Cytokine enhancement of DNA immunization leads to effective treatment of established pulmonary metastases. J Immunol 156:238–245, 1996.
Hock H, Dorsch M, Kunzendorf V et al: Mechanismus of vejection induced by tumor cell-targeted gene transfer of interleukin 2, interleukin 4, interleukin 7, tumor necrosis factor or interferon gamma. Proc Natl Acad Sci USA 90:2774–2778, 1993.
Jacob L, Somasundaram R, Smith W et al: Cytotoxic T-cell clone against rectal carcinoma induced by stimulation of a patient’s peripheral blood mononuclear cells with autologous cultured tumor cells. Int J Cancer 71:325–332, 1997.
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.
Jager E, Ringhoffer M, Karbach J et al: Inverse relationship of melanocyte differentiation antigen expression in melanoma tissues and CD8+ cytotoxic-T-cell responses: evidence for immunoselection of antigen-loss variants in vivo. Int J Cancer 66:470–476, 1996.
Jesdale BM, Deocampo G, Meisell J, et al: Matrix-based predicition of MHC-binding peptides: the EpiMatrix algorithm, reagent for HIV research In: Vaccines 97. Cold Spring Harbor Laboratory Press, 1997, pp. 1–7. http://www.epimatrix.com/HIV/.
Kang X, Kawakami Y, el-Gamil M et al: Identification of a tyrosinase epitope recognized by HLA-A24-restricted, tumor-infiltrating lymphocytes. J Immunol 155:1343–1348, 1995.
Kaufman H, Schlom J, and Kantor J: A recombinant vaccinia virus expressing human carcinoembryonic antigen (CEA). Int J Cancer 48:900–907, 1991.
Kawakami Y, Eliyahu S, Delgado CH et al: Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci USA 91:3515–3519, 1994.
Kawakami Y, Eliyahu S, Delgado CH et al: Identification of a human melanoma antigen recognized by tumor-infiltrating lym-phocytes associated with in vivo tumor rejection. Proc Natl Acad Sci USA 91:6458–6462, 1994.
Kawakami Y, Eliyahu S, Sakaguchi K et al: Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-2-restricted tumor infiltrating lymphocytes. J Exp Med 180:347–352, 1994.
Knight BC, Souberbielle BE, Rizzardi GP et al: Allogeneic murine melanoma cell vaccine: a model for the development of human allogeneic cancer vaccine. Melanoma Research. 6: 1–8, 1996.
Lethe B, van den Eynde B, Van Pel A et al: Mouse tumor rejection antigens P815A and P815B: two epitopes carried by a single peptide. Eur J Immunol 22:2283–2288, 1992.
Luescher IF, Romero P, Kuznetsov D et al: HLA photoaffinity labeling reveals overlapping binding of homologous melanoma-associated gene peptides by HLA-A1, HLA-A29, and HLA-B44. J Biol Chem 271:12463–12471, 1996.
Lurquin C, Van Pel A, Mariame B et al: Structure of the gene of turn-transplantation antigen P91 A: the mutated exon encodes a peptide recognized with Ld by cytolytic T cells. Cell 58:293–303, 1989.
Maass G, Schmidt W, Berger M et al: Priming of tumor-specific T cells in the draining lymph nodes after immunization with interleukin 2-secreting tumor cells: Three consecutive stages may be required for successful tumo r vaccination. Proc Natl Acad Sci USA 92:5540–5544, 1995.
Maeurer MJ, Gollin SM, Martin D et al: Tumor escape from immune recognition: lethal recurrent melanoma in a patient associated with downregulation of the peptide transporter protein TAP-1 and loss of expression of the immunodominant MART-1/Melan-A antigen. J Clin Invest 98:1633–1641, 1996.
Mandelboim O, Vadai E, Fridkin M et al: Regression of established murine carcinoma metastases following vaccination with tumour-associated antigen peptides. Nature Med 1:1179–1183, 1995.
Mannering SI, McKenzie JL, Fearnley DB et al: HLA-DRl-restricted bcr-abl (b3a2)-specific CD4+ T lymphocytes respond to dendritic cells pulsed with b3a2 peptide and antigen-presenting cells exposed to b3a2 containing cell lysates. Blood 90:290–297, 1997.
Marchand M, Weynants P, Rankin E et al: Tumor regression responses in melanoma patients treated with a peptide encoded by gene MAGE-3. Int J Cancer 63:883–885, 1995.
Matzinger P: Tolerance,danger, and the extended family. Annu Rev Immunol 12:991–1045, 1994.
Mazzocchi A, Storkus WJ, Traversari C et al: Multiple melanoma-associated epitopes recognized by HLA-A3-restricted CTLs and shared by melanomas but not melanocytes. J Immunol 157:3030–3038, 1996.
McHeyzer-Williams MG, Altman JD, and Davis MM: Tracking antigen-specific helper T cell responses. Curr Opin Immunol 8:278–284, 1996.
Mclntyre CA, Reees RC, Platts KE et al: Identification of peptide epitopes of MAGE-1,-2,-3 that demonstrate HLA-A3-specific binding. Cancer Immunol Immunother 42:246–250, 1996.
Meadows L, Wang W, den Haan JM et al: The HLA-A*0201-restricted H-Y antigen contains a posttranslationally modified cysteine that significantly affects T cell recognition. Immunity 6:273–281, 1997.
Mizoguchi H, O’Shea JJ, Longo DL et al: Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice [see comments]. Science 258:1795–1798, 1992.
Musani P, Modesti A, Giovarelli M et al: Cytokines, tumor cell death and immunogenicity: a question of choice. Immunology Today 18:32–36, 1997.
Noguchi Y, Richards EC, Chen YT et al: Influence of interleukin 12 on p53 peptide vaccination against established Meth A sarcoma. Proc Natl Acad Sci USA 92:2219–2223, 1995.
Oettgen HF, Old LJ: The history of cancer immunotherapy. In: Biologic therapy of cancer, principles and practice. (Eds: De Vita VT, Helman S, Rosenberg SA) JB Lippincott, 1991, pp. 87–119.
Ottenhoff THM, Geluk A, Toebes M et al: A sensitive fluorometric assay for quantitatively measuring specific peptide binding to HLA class I and class II molecules. J Immunol Methods 200:89–97, 1997.
Pan ZK, Ikonomidis G, Lazenby A et al: A recombinant Listeria monocytogenes vaccine expressing a model tumour antigen protects mice against lethal tumour cell challenge and causes regression of established tumours. Nature Med 1:471–477, 1995.
Pardoll DM: Paracrine cytokine adjuvants in cancer immunotherapy. Ann Rev Immunol 13:399–415, 1995.
Pardoll DM and Beckerleg AM: Exposing the immunology of naked DNA vaccines. Immunity 3:165–169, 1995.
Parker KC, Shields M, DiBrino M et al: Peptide binding to MHC class I molecules: implications for antigenic peptide prediction. Immunol Res 14:34–57, 1995. http://bimas.dcrt.nih.gov/molbio/hla_bind/
Parkhurst MR, Salgaller ML, Southwood S et al: Improved induction of melanoma-reactive CTL with peptides from the melanoma antigen gp 100 modified at HLA-A*0201-binding residues. J Immunol 157:2539–2548, 1996.
Prehn RT: Immunity to methylcholantrene-induced sarcomas. J Natl Cancer Inst 18:769–778, 1957.
Puccetti P, Bianchi R, Fioretti MC et al: Using a skin test assay to determine tumor-specific CD8+ reactivity. Eur J Immunol 24:1446–1452, 1994.
Rammensee HG, Falk K, and Rotzschke O: Peptides naturally presented by MHC class I molecules. Annu Rev Immunol 11:213–244, 1993.
Rammensee HG, Friede T, and Stevanovic S: MHC ligands and peptide motifs: first listing. Immunogenetics 41:178–228, 1995.
Ressing ME, Sette A, Brandt RM et al: Human CTL epitopes encoded by human papillomavirus type 16 E6 and E7 identified through in vivo and in vitro immunogenicity studies of HLA-A*0201-binding peptides. J Immunol 154:5934–5943, 1995.
Restifo NP: The new vaccines: building viruses that elicit antitumor immunity. Curr Opin Immunol 8:658–663, 1996.
Rettig WJ and Old LJ: Immunogenetics of human cell surface differentiation. Ann Rev Immunol 7:481–511, 1989.
Robbins PF, el-Gamil M, Li YF et al: A mutated beta-catenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes. J Exp Med 183:1185–1192, 1996.
Robbins PF, el-Gamil M, Li YF et al: Cloning of a new gene encoding an antigen recognized by melanoma-specific HLA-A24-restricted tumor-infiltrating lymphocytes. J Immunol 154:5944–5950, 1995.
Rock KL: A new foreign policy: MHC class I molecules monitor the outside world. Immunology Today 17:131–137, 1996.
Rosenberg SA: Cancer vaccines based on the identification of genes encoding cancer regression antigens. Immunol Today 4:175–182, 1997.
Rosenberg SA, Lotze MT, and Mule JJ: New approaches to the immunotherapy of cancer using interleukin-2. Ann Intern Med 108:853–864, 1988.
Rosenberg SA, Packard BS, and Aebersold PM: Special report: use of tumor infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med 319:1676–1680, 1988.
Roth C, Rochlitz C, and Kourilsky P: Immune response against tumors. Adv Immunol 57:281–351, 1994.
Rous P: An experimental comparison of transplanted tumor and a transplanted normal tissue capable of growth. J Exp Med 12:344–365, 1910.
Röcken M, Urban JE and Shevach EM: Infection breaks T cell tolerance. Nature 359:79–82, 1992.
Sahin U, Tureci O, Schmitt H et al: Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci USA 92:11810–11813, 1995.
Salgaller ML: Monitoring of cancer patients undergoing active or passive immunotherapy. J Immunother 20:1–14, 1997.
Schlegel PG, Aharoni R, Chen Y et al: A synthetic random basic copolymer with promiscuous binding to class II major histocompatibility complex molecules inhibits T-cell proliferative responses to major and minor histocompatibility antigens in vitro and confers the capacity to prevent murine graft-versus-host disease in vivo. Proc Natl Acad Sci USA 93:5061–5066, 1996.
Schmidt W, Buschle M, Zauner W et al: Cell-free tumor antigen peptide-based cancer vaccines. Proc Natl Acad Sci USA 94:3262–3267, 1997.
Schmidt W, Steinlein P, Buschle M et al: Transloading of tumor cells with foreign MHC I peptide ligand: a novel general strategy for the generation of potent cancer vaccines. Proc Natl Acad Sci USA 93:9759–9763, 1996.
Schweighoffer T: Tumor cells expressing a recall antigen are powerful cancer vaccines. Eur J Immunol 26:2559–2564, 1996.
Schweighoffer T, Berger M, Buschle M et al: Adenovirus-enhanced receptor-mediated transferrinfection for the generation of tumor vaccines. Cytokines and Molecular Therapy 2/3:185–191, 1996.
Sette A, Sidney J, del Guercio MF et al: Peptide binding to the most frequent HLA-A class I alleles measured by quantitative molecular binding assays. Mol Immunol 31:813–822, 1994.
Sette A, Vitiello A, Reherman B et al: The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J Immunol 153:5586–5592, 1994.
Shen R, Su ZZ, Olsson CA et al: Identification of the human prostatic carcinoma oncogene PTI-1 by rapid expression cloning and differential RNA display. Proc Natl Acad Sci USA 92:6778–6782, 1995.
Sibille C, Chomez P, Wildmann C et al: Structure of the gene of turn-transplantation antigen P198: a point mutation generates a new antigenic peptide. J Exp Med 172:35–45, 1990.
Sidney J, Grey HM, Kubo RT et al: Practical, biochemical and evolutionary implications of the discovery of HLA class I supermotifs. Immunology Today 17:261–266, 1996.
Skipper JCA, Hendrickson RC, Gulden PH et al: An HLA-A2-restricted tyrosinase antigen on melanoma cells results from posttranslational modification and suggests a novel pathway for processing of membrane proteins. J Exp Med 183:527–534, 1996.
Song ES, Lee V, Surh CD et al: Antigen presentation in retroviral vector-mediated gene transfer in vivo. Proc Natl Acad Sci USA 94:1943–1948, 1997.
Szikora JP, Van Pel A, and Boon T: Turn-mutation P35B generates the MHC-binding site of a new antigenic peptide. Immunogenetics 37:135–138, 1993.
Tan KC, Hosoi J, Grabbe S et al: Epidermal cell presentation of tumor-associated antigens for induction of tolerance. J Immunol 153:760–767, 1994.
Tepper RI and Mule JJ: Experimental and clinical studies of cytokine gene-modified tumor cells. Review. Human Gene Therapy 5:153–164, 1994.
Tepper RI, Pattengale PK, and Leder P: Murine Interleukin-4 displays potent anti-tumor activity in vivo. Cell 57:503–512, 1989.
Theobald M, Biggs J, Dittmer D et al: Targeting p53 as a general tumor antigen. Proc Natl Acad Sci USA 92:11993–11997, 1995.
Toes REM, Blom RJJ, Offringa R et al: 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.
Topalian SL, Rivoltini L, Mancini M et al: Human CD4+ T cells specifically recognize a shared melanoma-associated antigen encoded by the tyrosinase gene. Proc Natl Acad Sci USA 91:9461–9465, 1994.
Townsend AR, Rothbard J, Gotch FM et al: The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44:959–968, 1986.
Tsang KY, Zaremba S, Nieroda CA et al: Generation of human cytotoxic T cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia-CEA vaccine. J Natl Cancer Inst 87:982–990, 1995.
Tureci O, Sahin U, Schobert I et al: The SSX-2 gene, which is involved in the t(X;18) translocation of synovial sarcomas, codes for the human tumor antigen HOM-MEL-40. Cancer. Res 56:4766–4772, 1996.
Tureci O, Schmitt H, Fadle N et al: Molecular Definition of a Novel Human Galectin Which Is Immunogenic in Patients with Hodgkin’s Disease. J Biol Chem 272:6416–6422, 1997.
Ulmer JB, Donnelly JJ, Parker SE et al: Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259:1745–1749, 1993.
Valmori D, Lienard D, Waanders G et al: Analysis of MAGE-3-specific cytolytic T lymphocytes in human leukocyte antigen-A2 melanoma patients. Cancer Res 57:735–741, 1997.
van den Eynde B, Lethe B, Van Pel A et al: The gene coding for a major tumor rejection antigen of tumor P815 is identical to the normal gene of syngeneic DBA/2 mice. J Exp Med 173:1373–1384, 1991.
van den Eynde B, Mazarguil H, Lethe B et al: Localization of two cytotoxic T lymphocyte epitopes and three anchoring residues on a single nonameric peptide that binds to H-2Ld and is recognized by cytotoxic T lymphocytes against mouse tumor P815. Eur J Immunol 24:2740–2745, 1994.
van den Eynde B, Peeters O, De Backer O et al: A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med 182:689–698, 1995.
van der Bruggen P, Bastin J, Gajewski T et al: A peptide encoded by human gene MAGE-3 and presented by HLA-A2 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3. Eur J Immunol 24:3038–3043, 1994.
van der Bruggen P, Szikora JP, Boel P et al: Autologous cytolytic T lymphocytes recognize a MAGE-1 nonapeptide on melanomas expressing HLA-Cw*1601*. Eur J Immunol 24:2134–2140, 1994.
van der Bruggen P, Traversari C, Chomez P et al: A gene encoding an antigen recognised by cytolytic T lymphocytes on a human melanoma. Science 2:1643–1647, 1991.
van der Burg SH, Visseren MJ, Brandt RM et al: Immunogenicity of peptides bound to MHC class I molecules depends on the MHC-peptide complex stability. J Immunol 156:3308–3314, 1996.
Vitiello A, Ishioka G, Grey HM et al: Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans. J Clin Invest 95:341–349, 1995.
Vitiello A, Sette A, Yuan L et al: Comparison of cytotoxic T lymphocyte responses induced by peptide or DNA immunization: implications on immunogenicity and immunodominance. Eur J Immunol 27:671–678, 1997.
Wang RF, Appella E, Kawakami Y et al: Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes. J Exp Med 184:2207–2216, 1996.
Wang RE, Parkhurst M, Kawakami Yet al: Utilization of an alternative open reading frame of a normal gene in generating a novel human cancer antigen. J Exp Med 183:1131–1140, 1996.
Wang RF, Robbins PF, Kawakami Y et al: Identification of a gene encoding a melanoma tumor antigen recognized by HLA-A31-restricted tumor-infiltrating lymphocytes. J Exp Med 181:799–804, 1995.
Wentworth PA, Vitiello A, Sidney J et al: Differences and similarities in the A2.1-restricted cytotoxic T cell repertoire in humans and human leukocyte antigen-transgenic mice. Eur J Immunol 26:97–101, 1996.
Widmann C, Romero P, Maryanski JL et al: T helper epitopes enhance the cytotoxic response of mice immunized with MHC class I-restricted malaria peptides. J Immunol Methods 155:95–99, 1992.
Wolfel T, Hauer M, Schneider J et al: A pl6INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 269:1281–1284, 1995.
Wolfel T, Klehmann E, Muller C et al: Lysis of human melanoma cells by autologous cytolytic T cell clones. Identification of human histocompatibility leukocyte antigen A2 as a restriction element for three different antigens. J Exp Med 170:797–810, 1989.
Wolfel T, Van Pel A, Brichard V et al: Two tyrosinase nonapeptides recognized on HLA-A2 melanomas by autologous cytolytic T lymphocytes. Eur J Immunol 24:759–764, 1994.
Wortzel RD, Phillips C, and Schreiber H: Multiple tumor-specific antigens expressed on a single tumor cell. Nature 304:165–167, 1983.
Wu TC, Huang AYC, Jaffee EM et al: A reassessment of the role of B7-1 expression in tumor rejection. J Exp Med 182:1415–1421, 1995.
Zinkernagel RM and Doherty PC: Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 248:701–702, 1973.
Zitvogel L, Mayordomo JI, Tjandrawan T et al: Therapy of murine tumors with tumor peptide-pulsed dendritic cells: dependence on T cells, B7 costimulation, and T helper cell 1-associated cytokines. J Exp Med 183:87–97, 1996.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Schweighoffer, T. Molecular cancer vaccines: Tumor therapy using antigen-specific immunizations. Pathol. Oncol. Res. 3, 164–176 (1997). https://doi.org/10.1007/BF02899917
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02899917