Simultaneous CD8+ T cell responses to multiple tumor antigen epitopes in a multipeptide melanoma vaccine.

Abstract

The recent identification and molecular characterization of tumor-associated antigens recognized by tumor-reactive CD8+ T lymphocytes has led to the development of antigen-specific immunotherapy of cancer. Among other approaches, clinical studies have been initiated to assess the in vivo immunogenicity of tumor antigen-derived peptides in cancer patients. In this study, we have analyzed the CD8+ T cell response of an ocular melanoma patient to a vaccine composed of four different tumor antigen-derived peptides administered simultaneously in incomplete Freund's adjuvant (IFA). Peptide NY-ESO-1(157-165) was remarkably immunogenic and induced a CD8+ T cell response detectable ex vivo at an early time point of the vaccination protocol. A CD8+ T cell response to the peptide analog Melan-A(26-35 A27L) was also detectable ex vivo at a later time point, whereas CD8+ T cells specific for peptide tyrosinase(368-376) were detected only after in vitro peptide stimulation. No detectable CD8+ T cell response to peptide gp100(457-466) was observed. Vaccine-induced CD8+ T cell responses declined rapidly after the initial response but increased again after further peptide injections. In addition, tumor antigen-specific CD8+ T cells were isolated from a vaccine injection site biopsy sample. Importantly, vaccine-induced CD8+ T cells specifically lysed tumor cells expressing the corresponding antigen. Together, these data demonstrate that simultaneous immunization with multiple tumor antigen-derived peptides can result in the elicitation of multiepitope-directed CD8+ T cell responses that are reactive against antigen-expressing tumors and able to infiltrate antigen-containing peripheral sites.

• Authors: Danila Valmori, Valérie Dutoit, Maha Ayyoub, Donata Rimoldi, Philippe Guillaume, Danielle Liénard, Ferdy Lejeune, Jean-Charles Cerottini, Pedro Romero, Daniel E Speiser
• Journal: Cancer immunity (Cancer Immun) Vol. 3 Pg. 15 (Oct 28 2003) ISSN: 1424-9634 [Electronic] United States
• PMID: 14580186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• CTAG1B protein, human
• Cancer Vaccines
• Epitopes, T-Lymphocyte
• HLA-A2 Antigen
• Lipids
• MART-1 Antigen
• MLANA protein, human
• Membrane Proteins
• Neoplasm Proteins
• Peptide Fragments
• Proteins
• Vaccines, Subunit
• incomplete Freund's adjuvant
• Freund's Adjuvant
• Monophenol Monooxygenase

Topics

• Antigens, Neoplasm (administration & dosage, immunology)
• CD8-Positive T-Lymphocytes (chemistry, immunology)
• Cancer Vaccines (administration & dosage, immunology)
• Cytotoxicity Tests, Immunologic (methods)
• Drug Administration Schedule
• Epitopes, T-Lymphocyte (administration & dosage, immunology)
• Freund's Adjuvant (administration & dosage, immunology)
• HLA-A2 Antigen (administration & dosage, immunology)
• Humans
• Injections, Subcutaneous
• Lipids (administration & dosage, immunology)
• Longitudinal Studies
• Lymphocyte Activation (immunology)
• MART-1 Antigen
• Melanoma (immunology, prevention & control)
• Membrane Proteins
• Monophenol Monooxygenase (administration & dosage, chemistry, immunology)
• Neoplasm Proteins (immunology)
• Peptide Fragments (administration & dosage, immunology)
• Proteins (administration & dosage, immunology)
• T-Lymphocytes, Cytotoxic (chemistry, immunology)
• Tumor Cells, Cultured
• Uveal Neoplasms (immunology, prevention & control)
• Vaccines, Subunit (administration & dosage, immunology)