Novel Immune-Modulating Cellular Vaccine for Prostate Cancer Immunotherapy
Annual rept. 30 Sep 2014-29 Sep 2015
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 PAPspecific immunization using RNA-transfected DCs elicits robust and superior functional T cell responses in TRAMP mice. Using human cells, we have performed FDA mandated validation of DC-PAPvac-C to confirm anti-CTLA4 mAb expression and PAP presentation by human DCs transfected with mRNA encoding human PAP and antihuman CTLA4. Finally, we have completed the three cGMP production runs including lot release testing of the final DC-PAPvac-C cellular vaccine product.
- Medicine and Medical Research