Novel Immune Modulating Cellular Vaccine for Prostate Cancer Immunotherapy
Abstract
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 PD1/PDL1 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 PD1/PDL1 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2016
- Accession Number
- AD1024724
Entities
People
- Smita K Nair
Organizations
- Duke University Hospital