) Prostate cancers express tissue-specific differentiation antigens that might be able to target highly selective autoimmune T cell immune responses with the ability to eliminate malignantly transformed cells. The purpose of the current study is to determine whether a synthetic peptide corresponding to a defined T cell epitope within prostate-specific antigen is able to elicit anti-tumor immunity in patients with locally advanced or metastatic, hormone- sensitive prostate cancer. A nonameric PSA peptide with high affinity for HLA-A2 and the ability to elicit HLA-A2 restricted T cells will be used to immunize patients with locally advanced tumors at high risk of recurrence or hormone-sensitive metastatic prostate cancers. The proposal addresses the hypothesis that a PSA peptide administered with autologous dendritic cells or an adjuvant designed to promote dendritic cell maturation and function in vivo will induce peptide-specific T cells and will mediate potent anti-tumor effects.
The specific aims of the proposal are: 1) To determine the ability of PSA-peptide vaccinations to induce or enhance short- and long-term PSA- specific T cell immunity (cytolytic, proliferative, cytokine release) in prostate cancer patients; 2) To determine the ability of PSA-peptide- vaccinations in prostate cancer patients to induce or enhance the development of cytolytie T lymphocytes (CIL) capable of lysing HLA-A2+ tumors which endogenously express PSA protein; 3) To determine the elinical disease course of prostate cancer in vaccinated patients with stage B2/C or D1/D2 hormone- sensitive prostate cancers; and 4) To determine whether patients who demonstrate clinically progressive disease following PSA-peptide based vaccination develop PSA- or HLA-A2- loss variants in their progressive cancer as a potential mechanism of immune escape and disease progression.
| Perambakam, Supriya; Xie, Hui; Edassery, Seby et al. (2010) Long-term follow-up of HLA-A2+ patients with high-risk, hormone-sensitive prostate cancer vaccinated with the prostate specific antigen peptide homologue (PSA146-154). Clin Dev Immunol 2010:473453 |
| Perambakam, Supriya; Hallmeyer, Sigrun; Reddy, Samarth et al. (2006) Induction of specific T cell immunity in patients with prostate cancer by vaccination with PSA146-154 peptide. Cancer Immunol Immunother 55:1033-42 |
| Perambakam, Supriya M; Srivastava, Richa; Peace, David J (2005) Distinct cytokine patterns exist in peripheral blood mononuclear cell cultures of patients with prostate cancer. Clin Immunol 117:94-9 |
| Perambakam, Supriya; Xue, Bao-Hua; Sosman, Jeffrey A et al. (2002) Induction of Tc2 cells with specificity for prostate-specific antigen from patients with hormone-refractory prostate cancer. Cancer Immunol Immunother 51:263-70 |
