Pretreatment antigen-specific immunity and regulation - association with subsequent immune response to anti-tumor DNA vaccination

J Immunother Cancer. 2017 Jul 18;5(1):56. doi: 10.1186/s40425-017-0260-3.


Background: Immunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics. In the current study, we sought to determine if measures of antigen-specific or antigen non-specific immunity were present prior to treatment, and associated with subsequent immune response, to identify possible predictive immune biomarkers.

Methods: Patients who developed persistent PAP-specific, IFNγ-secreting immune responses were defined as immune "responders." The frequency of peripheral T cell and B cell lymphocytes, natural killer cells, monocytes, dendritic cells, myeloid derived suppressor cells, and regulatory T cells were assessed by flow cytometry and clinical laboratory values. PAP-specific immune responses were evaluated by cytokine secretion in vitro, and by antigen-specific suppression of delayed-type hypersensitivity to a recall antigen in an in vivo SCID mouse model.

Results: The frequency of peripheral blood cell types did not differ between the immune responder and non-responder groups. Non-responder patients tended to have higher PAP-specific IL-10 production pre-vaccination (p = 0.09). Responder patients had greater preexisting PAP-specific bystander regulatory responses that suppressed DTH to a recall antigen (p = 0.016).

Conclusions: While our study population was small (n = 38), these results suggest that different measures of antigen-specific tolerance or regulation might help predict immunological outcome from DNA vaccination. These will be prospectively evaluated in an ongoing randomized, phase II trial.

Keywords: Biomarker; DNA vaccine; Interleukin 10; Prostate cancer; Prostatic acid phosphatase.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acid Phosphatase / immunology*
  • Animals
  • Antigens, Neoplasm / immunology
  • Biomarkers, Tumor / immunology
  • Cancer Vaccines / immunology*
  • Humans
  • Immunity, Cellular / immunology*
  • Immunogenicity, Vaccine
  • Immunophenotyping
  • Interferon-gamma / immunology
  • Interleukin-10 / biosynthesis
  • Leukocyte Count
  • Leukocytes, Mononuclear / immunology
  • Male
  • Mice, SCID
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / therapy
  • Vaccines, DNA / immunology*
  • Vaccines, DNA / therapeutic use


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cancer Vaccines
  • Vaccines, DNA
  • Interleukin-10
  • Interferon-gamma
  • Acid Phosphatase
  • prostatic acid phosphatase