Optimization of Peptide Based Vaccines for Cancer

Project: Research project

Project Details


Optimization of Peptide Based Vaccines for Cancer. The successful identification of numerous T cell
epitopes derived from tumor-associated antigens has opened the doors to the development of subunit
vaccines for the treatment and prevention of cancer. Vaccines prepared from synthetic peptides representinc
these T cell epitopes constitute an attractive approach for the induction of anti-tumor immune responses
because they are easily manufactured, they are simple to characterize, they are relatively stable and most
importantly, they are extremely cost effective as compared to other types of vaccines. However, peptide-
based vaccines are not very immunogenic and so far the results in the clinic have been somewhat
disappointing. We hypothesize that peptide vaccines fail to induce the robust T cell responses that are
required to attain anti-tumor effects, because they lack the "danger signals" necessary that awaken the
immune system. Moreover, most peptide vaccines tested so far have been designed to stimulate cytotoxic T
lymphocytes (CTL) and have overlooked to trigger anti-tumor helper T lymphocyte (HTL) responses, which
we believe are necessary for the persistence of anti-tumor CTL function at the tumor site (secondary
hypothesis). In order to address these issues we propose to explore in an animal tumor model system the
following specific aims : 1) To evaluate various vaccine formulations and adjuvants for their capacity to elicit
CTL and HTL responses against peptide immunogens; 2) To assess the possibility of enhancing anti-tumor
T cell responses induced by peptide vaccination, by disrupting lymphocyte homeostasis; and 3) To study the
role of antigen-specific HTL in the survival and proliferative capacity of effector and memory CTL responses
against tumors. To accomplish these aims we have selected compounds and experimental approaches that
could be applied to human trials in an expedient manner. The completion of these studies should markedly
facilitate the translation of effective peptide vaccines into the clinic.
StatusNot started


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