Synthetic luteinizing hormone releasing hormone (LHRH) vaccine for effective androgen deprivation and its application to prostate cancer immunotherapy

Abstract

We have designed a peptide-based immunotherapeutic vaccine for treatment of androgen-responsive prostate cancer. The vaccine targets the luteinizing hormone-releasing hormone (LHRH) decapeptide that results in an androgen-deprivation immunotherapy. The design elements of the peptide immunogens are the LHRH peptide or B cell epitope synthetically linked to different promiscuous helper T cell (Th) sequences, the UBITh epitopes, derived from four natural pathogens for effective immunogenicity in outbred populations, and in some cases, also linked to an adjuvanting peptide from Yersinia invasin (Inv) protein. The UBITh LHRH immunogens are adsorbed on Alhydrogel or formulated as several different oil-based emulsions and tested in rodents, dogs, and a non-human primate, baboons. The immunogens generate an anti-LHRH antibody response specific to the LHRH decapeptide element in contrast to LHRH conjugate-carrier protein vaccines where only a small portion of the antibody response is directed to the target epitope and epitopic suppression is noted. Individual UBITh peptide domains, but not the LHRH and Inv peptide domains, are stimulatory in lymphocyte cultures. The UBITh LHRH immunogens in a clinically applicable formulation, controlled the growth of Dunning R3327-H androgen-responsive prostate tumor cells in rats. The results demonstrate universal responsiveness and long duration of androgen deprivation from three diverse species, and thus vaccine efficacy.