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 representing 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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA103921-02
Application #
7027988
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Hecht, Toby T
Project Start
2004-09-01
Project End
2009-08-31
Budget Start
2005-03-16
Budget End
2005-08-31
Support Year
2
Fiscal Year
2004
Total Cost
$203,456
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Pediatrics
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
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