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Novel Immune Modulating Cellular Vaccine for Prostate Cancer Immunotherapy

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Technical Report,30 Sep 2015,29 Sep 2016

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Duke University Medical Center Durham United States

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We have developed a novel strategy that combines tumor immunotherapy targeting PAP and targeted immune modulation of CTLA4 and have generated a lead cellular therapy that will safely enhance vaccine-mediated immunity. This lead cellular therapy, called DC-PAPvac-C, consists of dendritic cells DCs co-transfected with prostate tumor antigen, PAP RNA and anti-CTLA4 RNA. In this study we will establish the preclinical efficacy and safety of our cellular therapy product, DCs transfected with RNA that encodes PAP and anti-CTLA4 and generate data required for an Investigational New Drug IND application. In this report we have demonstrated that local CTLA4 modulation in combination with PAP-specific immunization using RNA-transfected DCs elicits superior antigen-specific T cell responses in TRAMP mice. We have now demonstrated that PD1PDL1 blockade synergizes with our novel vaccine strategy that combines induction of tumor-specific T cells with local blockade of the inhibitory T cell receptor, CTLA4. DC vaccine with local CTLA4 blockade in combination with systemic PD1PDL1 blockade is more effective at induction of antigen-specific T cells than DC vaccine and local CTLA-4 blockade alone. We have completed the three cGMP production runs including lot release testing of the final DCPAPvac-C cellular vaccine product.

Subject Categories:

  • Pharmacology
  • Medicine and Medical Research
  • Biochemistry

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