Our goal is to develop an effective vaccine for prostate cancer. Such a vaccine must stimulate CD8+ T cells against multiple prostate cancer antigens; as this is more likely to kill cancer cells and to circumvent heterogeneity in the expression of tumor antigens. To satisfy these requirements, we plan to construct a vaccine from multiple prostate cancer-associated peptides that are recognized by human CD8+ T cells and to encapsulate them into a novel and potent adjuvant (IL-2 liposomes).
Our specific aims are to: 1) Construct a prostate cancer vaccine from six HLA-A*020l restricted peptides that are recognized by human CD8+ T cells and that are derived from four (PSA, PSMA, MUC-l and CEA) prostate cancer associated antigens: all encapsulated into IL-2 liposomes. The vaccine will contain, as a positive control, an immunogenic, A*0201 restricted, flu peptide. 2) Examine the ability of the vaccine to stimulate anti-prostate cancer CD8 + T cell, CTL, DTH and antibody responses. 3) Evaluate the safety of the vaccine. The vaccine will be encapsulated into IL-2 liposomes using procedures that we have already perfected. Patients with prostate cancer who have biochemical recurrence after local therapy, and are HLA-A*020l positive, will he sequentially allocated to one of 4 treatment groups of 8 patients each. Each group will be immunized intradermally to one of 4 doses of vaccine (10g, 30ug, l00ug, 300ug of each peptide/immunization) in IL-2 liposomes, using a standard schedule. The primary end-points will be: a) Vaccine-induced stimulation of CD8+ T cells to the peptides used to construct the vaccine measured by ELISPOT; and b) toxicity measured by standard criteria. Secondary end-points will be vaccine-induced CTL, DTH and antibody responses. Based on 8 patients entered into each group, the trial will have 80 percent power to detect with a significance level of 0.05, differences of two and a half fold or greater in the magnitude of immune responses between groups. Smaller differences are unlikely to be clinically relevant. Successful completion of this work may provide a new treatment for prostate cancer that has minimal toxicity, that improves quality of life, and that has the ultimate potential to prevent this cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA090562-03
Application #
6859403
Study Section
Special Emphasis Panel (ZRG1-CONC (01))
Program Officer
Xie, Heng
Project Start
2002-07-01
Project End
2006-12-31
Budget Start
2005-01-01
Budget End
2005-12-31
Support Year
3
Fiscal Year
2005
Total Cost
$376,025
Indirect Cost
Name
New York University
Department
Dermatology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016