title: First-in-man application of a novel therapeutic cancer vaccine formulation with the capacity to induce multi-functional T cell responses in ovarian, breast and prostate cancer patients.
abstract: BACKGROUND
  DepoVax 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.
  
  
  METHODS
  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
  DPX-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.
  
  
  CONCLUSIONS
  The 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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01095848.
authors.affiliation: Sunnybrook Health Sciences Center, Toronto, ON, Canada.
authors.forename: Neil L
authors.initials: NL
authors.lastname: Berinstein
authors.forename: Mohan
authors.initials: M
authors.lastname: Karkada
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
authors.forename: John J
authors.initials: JJ
authors.lastname: Nemunaitis
authors.forename: Gurkamal
authors.initials: G
authors.lastname: Chatta
authors.forename: Howard
authors.initials: H
authors.lastname: Kaufman
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
authors.forename: Rita
authors.initials: R
authors.lastname: Nigam
authors.forename: Leeladhar
authors.initials: L
authors.lastname: Sammatur
authors.forename: Lisa D
authors.initials: LD
authors.lastname: MacDonald
authors.forename: Genevieve M
authors.initials: GM
authors.lastname: Weir
authors.forename: Marianne M
authors.initials: MM
authors.lastname: Stanford
authors.forename: Marc
authors.initials: M
authors.lastname: Mansour
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines