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

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

Author information

1
University of Wisconsin Carbone Cancer Center, 7007 Wisconsin Institutes for Medical Research, University of Wisconsin, Madison, 1111 Highland Avenue, Madison, WI, 53705, USA.
2
University of Wisconsin Carbone Cancer Center, 7007 Wisconsin Institutes for Medical Research, University of Wisconsin, Madison, 1111 Highland Avenue, Madison, WI, 53705, USA. dm3@medicine.wisc.edu.

Abstract

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

PMID:
28716080
PMCID:
PMC5514519
DOI:
10.1186/s40425-017-0260-3
[Indexed for MEDLINE]
Free PMC Article

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