An HLA-A2 polyepitope vaccine for melanoma immunotherapy.

Epitope-based vaccination strategies designed to induce tumor-specific CD8 CTL are being widely considered for cancer immunotherapy. Here we describe a recombinant poxvirus vaccine that codes for ten HLA-A2-restricted epitopes derived from five melanoma Ags conjoined in an artificial polyepitope or polytope construct. Target cells infected with the melanoma polytope vaccinia were recognized by three different epitope-specific CTL lines derived from HLA-A2 melanoma patients, and CTL responses to seven of the epitopes were generated in at least one of six HLA-A2-transgenic mice immunized with the construct. CTL lines derived from vaccinated transgenic mice were also able to kill melanoma cells in vitro. Multiple epitopes within the polytope construct were therefore shown to be individually immunogenic, illustrating the feasibility of the polytope approach for melanoma immunotherapy. Tumor escape from CTL surveillance, through down regulation of individual tumor Ags and MHC alleles, might be overcome by polytope vaccines, which simultaneously target multiple cancer Ags.

[1]  A. Suhrbier,et al.  Peptide based cytotoxic T-cell vaccines; delivery of multiple epitopes, help, memory and problems. , 1999, Vaccine.

[2]  B. Moss,et al.  Vaccination with a recombinant vaccinia virus encoding a "self" antigen induces autoimmune vitiligo and tumor cell destruction in mice: requirement for CD4(+) T lymphocytes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[3]  P. Gibbs,et al.  Spontaneous T cell responses to melanoma differentiation antigens from melanoma patients and healthy subjects , 1998, Cancer Immunology, Immunotherapy.

[4]  B. Bogen,et al.  Clonal deletion of thymocytes as a tumor escape mechanism , 1998, International journal of cancer.

[5]  Michael F. Good,et al.  Vaccine-induced cytotoxic T lymphocytes protect against retroviral challenge , 1998, Nature Medicine.

[6]  T. Sasazuki,et al.  Highly Restricted T Cell Repertoire Shaped by a Single Major Histocompatibility Complex–Peptide Ligand in the Presence of a Single Rearranged T Cell Receptor (cid:98) Chain , 1998 .

[7]  G. Parmiani,et al.  The susceptibility to natural killer cell‐mediated lysis of HLA class I‐positive melanomas reflects the expression of insufficient amounts of different HLA class I alleles , 1998, European journal of immunology.

[8]  Makiko Kobayashi,et al.  A pathogenic role of Th2 cells and their cytokine products on the pulmonary metastasis of murine B16 melanoma. , 1998, Journal of immunology.

[9]  M. Reddish,et al.  Anti‐MUC1 class I restricted CTLs in metastatic breast cancer patients immunized with a synthetic MUC1 peptide , 1998, International journal of cancer.

[10]  P. Cresswell,et al.  HLA-B27-restricted antigen presentation in the absence of tapasin reveals polymorphism in mechanisms of HLA class I peptide loading. , 1998, Immunity.

[11]  G. Fernando,et al.  Vaccine‐Induced Th1‐Type Responses are Dominant over Th2‐Type Responses in the Short Term whereas Pre‐existing Th2 Responses are Dominant in the Longer Term , 1998, Scandinavian journal of immunology.

[12]  F. Marincola,et al.  Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma , 1998, Nature Medicine.

[13]  Marion Becker,et al.  Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara , 1998, Nature Medicine.

[14]  M. Albert,et al.  Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs , 1998, Nature.

[15]  C. Melief,et al.  Specific T Helper Cell Requirement for Optimal Induction of Cytotoxic T Lymphocytes against Major Histocompatibility Complex Class II Negative Tumors , 1998, The Journal of experimental medicine.

[16]  Dirk Schadendorf,et al.  Vaccination of melanoma patients with peptide- or tumorlysate-pulsed dendritic cells , 1998, Nature Medicine.

[17]  Vasso Apostolopoulos,et al.  MUC1 cross-reactive Galα(l,3)Gal antibodies in humans switch immune responses from cellular to humoral , 1998, Nature Medicine.

[18]  D. Moss,et al.  Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination. , 1998, Journal of immunology.

[19]  D. Pardoll,et al.  Induction of antigen-specific T cell anergy: An early event in the course of tumor progression. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[20]  A. McMichael,et al.  Differential processing of influenza nucleoprotein in human and mouse cells , 1998, European journal of immunology.

[21]  C. Wilson,et al.  Autologous human monocyte-derived dendritic cells genetically modified to express melanoma antigens elicit primary cytotoxic T cell responses in vitro: enhancement by cotransfection of genes encoding the Th1-biasing cytokines IL-12 and IFN-alpha. , 1998, Journal of immunology.

[22]  J. Shabanowitz,et al.  The Class I Antigen-processing Pathway for the Membrane Protein Tyrosinase Involves Translation in the Endoplasmic Reticulum and Processing in the Cytosol , 1998, The Journal of experimental medicine.

[23]  F. Marincola,et al.  Immunodominance Across HLA Polymorphism: Implications for Cancer Immunotherapy , 1998, Journal of immunotherapy.

[24]  R. Offringa,et al.  Protective anti-tumor immunity induced by vaccination with recombinant adenoviruses encoding multiple tumor-associated cytotoxic T lymphocyte epitopes in a string-of-beads fashion. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[25]  E. Jaffee,et al.  Cancer Vaccines , 1997, Current protocols in human genetics.

[26]  F. Lemonnier,et al.  HLA-A2.1–restricted Education and Cytolytic Activity of CD8+ T Lymphocytes from β2 Microglobulin (β2m) HLA-A2.1 Monochain Transgenic H-2Db β2m Double Knockout Mice , 1997, The Journal of experimental medicine.

[27]  Lunli Yuan,et al.  Comparison of cytotoxic T lymphocyte responses induced by peptide or DNA immunization: Implications on immunogenicity and immunodominance , 1997, European journal of immunology.

[28]  P. Stern,et al.  Implications for immunosurveillance of altered HLA class I phenotypes in human tumours. , 1997, Immunology today.

[29]  S. H. van der Burg,et al.  Analogues of CTL epitopes with improved MHC class‐I binding capacity elicit anti‐melanoma CTL recognizing the wild‐type epitope , 1997, International journal of cancer.

[30]  A. Houghton,et al.  Immune response to a differentiation antigen induced by altered antigen: a study of tumor rejection and autoimmunity. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Simon C Watkins,et al.  DNA–based immunization by in vivo transfection of dendritic cells , 1996, Nature Medicine.

[32]  A Sette,et al.  Improved induction of melanoma-reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0201-binding residues. , 1996, Journal of immunology.

[33]  X. Mo,et al.  Recombinant polyepitope vaccines for the delivery of multiple CD8 cytotoxic T cell epitopes. , 1996, Journal of immunology.

[34]  J. Gralow,et al.  Peptide-based, but not whole protein, vaccines elicit immunity to HER-2/neu, oncogenic self-protein. , 1996, Journal of immunology.

[35]  J. Berzofsky,et al.  Selective expansion of high- or low-avidity cytotoxic T lymphocytes and efficacy for adoptive immunotherapy. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[36]  V. Engelhard,et al.  Importance of MHC class 1 alpha2 and alpha3 domains in the recognition of self and non-self MHC molecules. , 1996, Journal of immunology.

[37]  F. Brasseur,et al.  A peptide recognized by human cytolytic T lymphocytes on HLA-A2 melanomas is encoded by an intron sequence of the N- acetylglucosaminyltransferase V gene , 1996, The Journal of experimental medicine.

[38]  C. Uyttenhove,et al.  Endogenous IL-12 is necessary for rejection of P815 tumor variants in vivo. , 1996, Journal of immunology.

[39]  A. Vitiello,et al.  Differences and similarities in the A2.1‐restricted cytotoxic T cell repertoire in humans and human leukocyte antigen‐transgenic mice , 1996, European journal of immunology.

[40]  Rika Deraemaecker,et al.  Expression of MAGE genes in primary and metastatic cutaneous melanoma , 1995, International journal of cancer.

[41]  M. Salgaller,et al.  Recognition of multiple epitopes in the human melanoma antigen gp100 by peripheral blood lymphocytes stimulated in vitro with synthetic peptides. , 1995, Cancer research.

[42]  D J Moss,et al.  Minimal epitopes expressed in a recombinant polyepitope protein are processed and presented to CD8+ cytotoxic T cells: implications for vaccine design. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[43]  X. Sastre,et al.  Differences in the antigens recognized by cytolytic T cells on two successive metastases of a melanoma patient are consistent with immune selection , 1995, European journal of immunology.

[44]  P. Coulie,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 , 1994, European journal of immunology.

[45]  R. Ahmed,et al.  CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection , 1994, Journal of virology.

[46]  K. Sakaguchi,et al.  Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[47]  J. Renauld,et al.  A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas , 1994, The Journal of experimental medicine.

[48]  K. Sakaguchi,et al.  Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes , 1994, The Journal of experimental medicine.

[49]  B. Seliger,et al.  Two tyrosinase nonapeptides recognized on HLA‐A2 melanomas by autologous cytolytic T lymphocytes , 1994, European journal of immunology.

[50]  Günter J. Hämmerling,et al.  Selectivity of MHC-encoded peptide transporters from human, mouse and rat , 1994, Nature.

[51]  H. Jun,et al.  Cellular and molecular mechanisms for the initiation and progression of beta cell destruction resulting from the collaboration between macrophages and T cells. , 1998, Autoimmunity.

[52]  T. Blankenstein,et al.  B cells inhibit induction of T cell-dependent tumor immunity , 1998, Nature Medicine.

[53]  S. Burrows,et al.  Strategies involved in developing an effective vaccine for EBV-associated diseases. , 1996, Advances in cancer research.