Abstract
BackgroundDepoVaxTM is a novel non-emulsion depot-forming vaccine platform with the capacity to significantly enhance the immunogenicity of peptide cancer antigens. 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.MethodsA 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.ResultsDPX-0907 was shown to be safe with injection 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 were generally observed in patients with better disease control after their last prior treatment. Antigen-specific responses were detected in 73% of immune responders (44% of evaluable patients) after the first vaccination. In 83% of immune responders (50% of evaluable patients), peptide-specific T cell responses were detected at ≥2 time points post vaccination with 64% of the responders (39% of evaluable patients) 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.ConclusionsThe novel DepoVax formulation promotes multifunctional effector memory responses to peptide-based tumor associated antigens. The data supports the capacity of DPX-0907 to elicit Type-1 biased immune responses, warranting further clinical development of the vaccine. This study underscores the importance of applying vaccines in clinical settings in which patients are more likely to be immune competent.Trial RegistrationClinicalTrials.gov NCT01095848
Highlights
DepoVaxTM is a novel non-emulsion depot-forming vaccine platform with the capacity to significantly enhance the immunogenicity of peptide cancer antigens
These antigens are involved in multiple, critical cancer pathways such as tissue invasion and metastasis (P5; Integrin β8 subunit precursor, P14; Junction plakoglobin and P15; EDDR1), evading apoptotic cell death (P3; BAP31) and providing the ability to resist anti-growth signals (P7; Abl binding protein C3) [5,6,7,8,9], with resultant specific immune responses expected to reduce the chance for progression of tumor escape variants [9,10]
In order to enhance the potency of a peptide platform, we developed a novel vaccine platform called DepoVaxTM [11], a liposome-in-oil platform containing stable components that does not require creation of an emulsion, simplifying the use of oil-based depot vaccines in the clinic
Summary
DepoVaxTM is a novel non-emulsion depot-forming vaccine platform with the capacity to significantly enhance the immunogenicity of peptide cancer antigens. Our novel cancer vaccine DPX-0907 contains a polynucleotide-based adjuvant and a universal T helper peptide, along with seven HLA-A2 restricted peptides derived from tumor-associated antigens These antigens are involved in multiple, critical cancer pathways such as tissue invasion and metastasis (P5; Integrin β8 subunit precursor, P14; Junction plakoglobin and P15; EDDR1), evading apoptotic cell death (P3; BAP31) and providing the ability to resist anti-growth signals (P7; Abl binding protein C3) [5,6,7,8,9], with resultant specific immune responses expected to reduce the chance for progression of tumor escape variants [9,10]. Their inclusion in DPX-0907 yields an immunogenic vaccine in HLAA2 transgenic mice that promotes the activation of both Type 1 T cell responses, while minimizing the induction of regulatory mechanisms [11]
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