VACCINES WITH MHC CLASS II-RESTRICTED MELANOMA PEPTIDES

University Of Virginia Charlottesville, Charlottesville VA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Peptides derived from melanocyte differentiation proteins (MDP) and cancer testis antigens (CTA) have been synthesized and incorporated in human tumor vaccines, where cytotoxic T-cell responses have been induced in vivo in humans, and some clinical tumor regressions have been observed. The vast majority of peptide vaccines initiated to date worldwide have employed, short peptide epitopes for CTL. However, helper T-cell responses are important components of an integrated immune response. HTL can activate dendritic cells (DC) for heightened antigen presentation, causing the DC to secrete IL-2 and other cytokines that may help to direct the immune response. Furthermore, strong Th1 help produces the proper cytokine milieu, which is critical to the induction of immune mediated tumor destruction. In addition, HTL responses are believed to be involved in the establishment of memory responses. In the current application, we propose to test the safety and immunogenicity of vaccination with multiple peptide epitopes for HTL, which have recently been defined. The specific aims of the study are as follows: 1) To assess the safety of administration of escalating doses of multiple peptide epitopes for helper T lymphocytes (HTL), 2) To assess, in vitro, the immunogenicity of a vaccine that incorporates multiple peptide epitopes for helper T lymphocytes (HTL), and 3) To determine whether a vaccine combining multiple epitopes for HTL will induce delayed-type hypersensitivity responses to the immunizing peptides. [unreadable] [unreadable]