BACKGROUND:We developed a novel non-emulsion depot-forming vaccine platform called DepoVaxTM with the capacity to significantly enhance peptide cancer antigen immunogenicity.
METHODS:Naturally processed HLA-A2 restricted peptides presented by breast, ovarian and prostate cancer cells were used as antigens to create a therapeutic cancer vaccine, DPX-0907. A phase I clinical study was designed to examine the safety and immune activating potential of DPX-0907 in advanced stage breast, ovarian and prostate cancer patients. A total of 23 late stage cancer patients were recruited and were divided into two dose/volume cohorts in a three immunization protocol.
RESULTS:The DPX-0907 was shown to be safe with injected site reactions being the most commonly reported adverse event. All breast cancer patients (3/3), most of ovarian (5/6) and one third of prostate (3/9) cancer patients exhibited detectable immune responses, resulting in a 61% immunological response rate. Immune responses correlated with achievement of CR, PR or SD to previous treatment. Antigen-specific responses were detected in 73% of immune responders after the first vaccination. In 83% of immune responders, peptide-specific immunity was detected at [greater than or equal to]2 time points post vaccination with 64% of these individuals showing evidence of immune persistence. Immune monitoring also demonstrated the generation of antigen-specific T cell memory with the ability to secrete multiple Type 1 cytokines.
CONCLUSIONS: This study underscore the importance of applying vaccines in clinical settings in which patients are more likely to be immune competent. The novel DepoVax formulation promotes multifunctional effector memory responses to peptide-based tumor associated antigens. The data support the capacity of DPX-0907 to elicit Type-1 biased specific immunity, warranting further clinical development of the vaccine.
Written by:
Berinstein NL, Karkada M, Morse MA, Nemunaitis JJ, Chatta G, Kaufman H, Odunsi K, Nigam R, Sammatur L, Macdonald LD, Weir GM, Stanford MM, Mansour M. Are you the author?
Reference: J Transl Med. 2012 Aug 3;10(1):156.
doi: 10.1186/1479-5876-10-156
PubMed Abstract
PMID: 22862954
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