Abstract

Prostate cancer remains the second leading cause of cancer-related death in men in the United States. Conventional treatments as surgery, radiation and androgen suppression are effective if prostate cancer is confined to the prostate. Unfortunately, many patients with advanced metastatic cancer treated with androgen ablation experience recurrence of androgen-independent cancer, with limited or transient response to other systemic chemotherapies. The multiepitopic immunotherapy vaccine compositions fulfilled partially this need. Antigens that are associated with prostate cancer include, but are not limited to, prostate specific antigen (PSA), prostate specific membrane antigen (PSM), prostatic acid phosphatase (PAP), and human kallikrein2 (hK2 or HuK2). These antigens represent important antigen targets for the polyepitopic vaccine compositions of the invention. PSM is also an important candidate for prostate cancer therapy. It is a Type II membrane protein that is expressed at high levels on prostate adenocarcinomas. The levels of expression increase on metastases and in carcinomas that are refractory to hormone therapy. PSM is not generally present on normal tissues, although low levels have been detected in the colonic crypts and in the duodenum, and PSM can be detected in normal male serum and seminal fluid (see, e.g., Silver et al, Clin. Cancer Res. 3:81-85, 1997). PAP is a tissue-specific differentiation antigen that is secreted exclusively by cells in the prostate (see, e.g., Lam et al, Prostate 15:13-21, 1989). Prostate tumor PSA-dependent inhibition of PI3K produced dual but not optimal benefits for patients: by partially inhibiting the PI3K pathway at the tumor site and iin some cases not reducing side effects due to inhibition of PI3K in normal tissues, resulting only from the active drug being redistributed from the tumor. It is now widely acknowledged that the single target paradigm (i.e. one protein/target, one disease, one drug) that has been the dominant premise in drug development in recent past is untenable as both drug-like compound (ligand) and target protein can be promiscuous. Here, in Biogenea we have for the first time discovered a Novel Prostate Cancer-Targeted PI3 Kinase related PSA-PSM-PAP-Huk2-hK2 peptide derived motif like mimetic chemical Prodrug using the BiogenetoLigandorolTM and the MPINet cluster of algorithms.