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.
