Novel Immune Modulating Cellular Vaccine for Prostate Cancer
Annual rept. 30 Sept 2013 to 29 Sept 2014
DUKE UNIV MEDICAL CENTER DURHAM NC
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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. Importantly and relevant to our planned clinical trial implementation, we will develop a biomarker of therapeutic efficacy and demonstrate the feasibility of measuring these biomarkers. In this report we have demonstrated that local CTLA4 modulation in combination with PAP-specific immunization using RNA-transfected DCs elicits robust and superior functional T cell responses in TRAMP mice. We have also demonstrated that post-transcriptional modification of mRNAs to generate Cap1 mRNA enhances protein production by human DCs and human DCs transfected with Cap1 PAP mRNA without the signal sequence stimulate highest frequencies of PAP-specific T cells in an in vitro human immunotherapy assay.
- Medicine and Medical Research