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Published on: April 27, 2018
Eradication of pre-clinical prostate tumors by a lentiviral vector-based immunotherapy
Benjamin Vesin1, Ingrid Fert1, Sylvain Ciret1
1Pasteur-TheraVectys Joint Lab, Institut Pasteur, Université de Paris, Virology Department, 28 Rue Du Dr. Roux, 75015 Paris, France.
Abstract:
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.
Insights
A novel Lenti-PROST-02 immunotherapy eradicated advanced prostate tumors in preclinical models. This therapeutic vaccine harnesses the immune system, showing promise for treating resistant prostate cancer.
Area of Science:
- Oncology
- Immunology
- Gene Therapy
Background:
- Metastatic prostate cancer presents significant treatment challenges, especially for tumors resistant to androgen deprivation.
- Current therapeutic options for advanced prostate cancer are limited, necessitating novel treatment strategies.
Purpose of the Study:
- To develop and evaluate a novel non-integrative lentiviral vector, Lenti-PROST-02, for prostate cancer immunotherapy.
- To assess the efficacy of Lenti-PROST-02 in eradicating virulent prostate tumors and stimulating anti-tumor immunity.
Main Methods:
- Development of Lenti-PROST-02 encoding T cell immunodominant regions of prostatic acid phosphatase and prostate-specific antigen.
- Administration of Lenti-PROST-02 immunotherapy in a preclinical prostate tumor model.
- Analysis of immune responses, including CD8+ T cell activation, tumor infiltration, and microenvironment changes.
Main Results:
- Lenti-PROST-02 achieved complete tumor eradication in the majority of treated animals.
- Immunotherapy induced poly-functional CD8+ T cell responses and increased tumor-infiltrating CD8+ T cells.
- A "cold-to-hot" inflammatory switch in the tumor microenvironment was observed, alongside long-lasting immunity and prevention of tumor relapse.
Conclusions:
- Lenti-PROST-02 demonstrates significant potential as a therapeutic vaccine for prostate cancer immuno-oncotherapy.
- The vaccine effectively stimulates a robust and durable anti-tumor immune response.
- This approach offers a promising strategy for overcoming treatment resistance in advanced prostate cancer.
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