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Personalized neoantigen DNA vaccine + nivolumab + ipilimumab + PROSTVAC

Development stage
Unknown
Lead developer
Washington University School of Medicine
Modality
DNA Vaccines → Plasmid DNA → DNA Therapeutics → Nucleic Acid Therapeutics, Prophylactic Vaccines → Vaccines & Immunotherapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
Administration
Electroporation, Intravenous, Subcutaneous
01

Overview

This combination therapy is a multi-modal immunotherapy regimen designed for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). It integrates four distinct components to stimulate a robust anti-tumor immune response: a personalized neoantigen DNA vaccine, the recombinant viral vaccine PROSTVAC, and the dual immune checkpoint inhibitors nivolumab (Opdivo) and ipilimumab (Yervoy). The personalized DNA vaccine, which encodes approximately 20 patient-specific mutated epitopes, is delivered via Ichor Medical Systems' TriGrid electroporation technology to prime tumor-specific T cells. PROSTVAC targets the shared prostate-specific antigen (PSA) and incorporates co-stimulatory molecules (B7.1, ICAM-1, and LFA-3) to further boost the immune response. Nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) are added to overcome immunosuppressive mechanisms within the tumor microenvironment. This strategy aims to induce a synergistic effect by combining shared antigen and neoantigen targeting with the removal of immune checkpoints.

Brand names
OpdivoYervoyPROSTVAC
Other names
Personalized neoantigen DNA vaccine + Opdivo + Yervoy + PROSTVACPersonalized polyepitope DNA vaccine + nivolumab + ipilimumab + PROSTVAC
02

Targets

PDCD1 (Programmed cell death protein 1 receptor)MHC I (MHC class I})CD58 (Leukocyte function-associated antigen 3)CTLA-4 (Cytotoxic t-lymphocyte–associated protein 4)CD80 (T-lymphocyte activation antigen CD80)ICAM1 (Intercellular Adhesion Molecule 1)

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