Cancer Immunity 3:15 (2003)

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

Danila Valmori^1,4, Valérie Dutoit^1*, Maha Ayyoub^1,4*, Donata Rimoldi², Philippe Guillaume², Danielle Liénard^1,3, Ferdy Lejeune³, Jean-Charles Cerottini², Pedro Romero¹, and Daniel E. Speiser¹

¹Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, University Hospital (CHUV), 1011 Lausanne, Switzerland
²Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland
³Multidisciplinary Oncology Center, University Hospital (CHUV), 1011 Lausanne, Switzerland
⁴Ludwig Institute Clinical Trial Center at Division of Medical Oncology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA (current address)
^*These authors contributed equally to this work

Keywords: human, melanoma, vaccination, immunological monitoring, cytotoxic T cells

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.