Eradication of pre-clinical prostate tumors by a lentiviral vector-based immunotherapy.

Prostate cancer kills ≈350,000 yearly. While localized cases have 99% five-year survival, metastatic prostate cancer is hard to treat, with few options for tumors resistant to androgen deprivation. To leverage the immune system to fight prostate cancer, we developed a non-integrative lentiviral vector, namely "Lenti-PROST-02", which encodes clusters of T cell immunodominant regions of human prostatic acid phosphatase and prostate-specific antigen. Immunotherapy with Lenti-PROST-02 in a preclinical virulent prostate tumor model resulted in complete tumor eradication in vast majority of the treated animals. This antitumor effect was concomitant with induction of poly-functional CD8+ T splenocyte effectors against numerous T cell epitopes of the antigens encoded by Lenti-PROST-02, increased proportions of tumor-infiltrating CD8+ T cells with activated/differentiated/effector phenotype and a "cold-to-hot" inflammatory switch of the tumor microenvironment. Immunity induced by Lenti-PROST-02 was long-lasting and prevented tumor relapse. It was characterized by the persistence of CD44+ CD62L- CD127+ KLRG1- CD8+ memory T cells in secondary lymphoid organs, as well as an antigen-diversified memory response. Therefore, Lenti-PROST-02 therapeutic vaccine is a promising approach for prostate immuno-oncotherapy.