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Boosting immune response with GM-CSF optimizes primary cryotherapy outcomes in the treatment of prostate cancer: a prospective randomized clinical trial

Prostate Cancer and Prostatic Diseases volume 24, pages 750–757 (2021)Cite this article

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Abstract

Objective

We explored the association of prostate cryotherapy and immunomodulation with granulocyte-macrophage colony-stimulating factor (GMCSF) in the generation of detectable tumor-specific T- and B-cell responses in men with prostate cancer.

Materials and methods

A randomized pilot study of patients assigned to either cryotherapy alone (Control group) or in combination with GMCSF (Treatment group). The impact of therapy on the development of T- and B-cell responses against tumor-related antigens was studied using enzyme-linked immune absorbent spot (ELISpot) and protein microarray panels (Sematrix) assays, respectively. Fold changes in response to treatment were calculated by normalization of post-treatment ELISpot values against the mean pre-cryoablation response. Student t tests between treatment and control groups at 4 weeks and 12 weeks across all the antigens were performed.

Results

A total of 20 patients were randomized to either control or treatment arm. At 4 weeks after cryotherapy, the treatment group demonstrated an average fold change in cancer antigen-related antibodies of 2.8% above their mean baseline values, whereas controls averaged an 18% change below mean baseline (p < 0.05). At 12 weeks, antibody response in treatment group increased to 25% above baseline, while the average of control group patients remained 9% below baseline (p < 0.05). Patients in treatment group displayed, on average, higher ELISPOT readings for the 4- and 12-week times points (527 vs 481 for PSA and 748 vs 562 for PAP).

Conclusions

GMCSF appeared to broadly elevate antibodies against prostate-specific and nonspecific antigens. Prostate antigen-specific T-cell responses were more enhanced over non-prostate-specific responses, preferentially in the treatment group. Our findings suggest a possible therapeutic effect of adjuvant immunotherapy in association with cryotherapy for the treatment of prostate cancer.

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Fig. 1: Participant flowchart.
Fig. 2: Serum levels of antibodies against most significantly altered cancer-related antigens.
Fig. 3: ELISPOT analysis: frequency of T cell specific for prostate antigens (PAP and PSA).
Fig. 4: ELISPOT fold change.
Fig. 5: PSA response following treatment with cryotherapy alone and with the addition of GM-CSF.

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Funding

Unrestricted research grant, “Endocare Inc”

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Authors and Affiliations

  1. Division of Urology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Al Baha Barqawi, Rodrigo Rodrigues Pessoa & E. David Crawford

  2. Clinical Research and Trials Unit, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Mohammed Al-Musawi, Tracey MacDermott & Colin O’Donell

  3. Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Ross M. Kendl

Authors
  1. Al Baha Barqawi
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  4. Mohammed Al-Musawi
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Correspondence to Al Baha Barqawi.

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Barqawi, A.B., Rodrigues Pessoa, R., Crawford, E.D. et al. Boosting immune response with GM-CSF optimizes primary cryotherapy outcomes in the treatment of prostate cancer: a prospective randomized clinical trial. Prostate Cancer Prostatic Dis 24, 750–757 (2021). https://doi.org/10.1038/s41391-021-00321-8

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