Influence of Humoral Response Against GnRH, Generated by Immunization with a Therapeutic Vaccine Candidate on the Evolution of Patients with Castration-Sensitive Prostate Adenocarcinoma

Technol Cancer Res Treat. 2023 Jan-Dec:22:15330338231207318. doi: 10.1177/15330338231207318.

Abstract

Background and aims: A gonadotropin-releasing hormone (GnRH)-based therapeutic vaccine candidate against hormone-sensitive prostate cancer has demonstrated its safety and signs of efficacy in phase I/II trials. In this study, we characterized the isotype/subclass profiles of the anti-GnRH humoral response generated by the vaccination and analyzed its association with patients' clinical outcomes.

Methods: The immunoglobulin isotypes and IgG subclasses of the antibody responses of 34 patients included in a randomized, open, prospective phase I/II clinical trial were characterized. Every patient included in the study had a diagnosis of locally advanced prostate adenocarcinoma at stages 3 and 4 and received immunization with the vaccine candidate. Additionally, serum testosterone and prostate specific antigen (PSA) concentrations, serving as indicators of tumor response, were determined. The type of anti-GnRH antibody response was correlated to the time elapsed until the first biochemical recurrence in patients and the outcome of the disease.

Results: All patients developed strong and prolonged anti-GnRH antibody responses, resulting in a short- to mid-term decrease in serum testosterone and PSA levels. Following immunizations, anti-GnRH antibodies of the IgM/IgG and IgG1/IgG3 subclasses were observed. Following radiotherapy, the humoral response switched to IgG (IgG1/IgG4). Patients who experienced a short-term biochemical relapse were characterized by significantly higher levels of anti-GnRH IgG titers, particularly IgG1 and IgG4 subclasses. These characteristics, along with a high response of specific IgM antibodies at the end of immunizations and the development of anti-GnRH IgA antibody responses following radiotherapy, were observed in patients whose disease progressed, compared to those with controlled disease.

Conclusion: The nature of the humoral response against anti-GnRH, induced by vaccination may play a key role in activating additional immunological mechanisms. Collectively, these mechanisms could contribute significantly to the regulation of tumor growth.

Keywords: GnRH-based vaccine; anti-GnRH response; castration-sensitive prostate cancer; immunoglobulin isotypes; therapeutic vaccine.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adenocarcinoma* / therapy
  • Castration
  • Gonadotropin-Releasing Hormone
  • Humans
  • Immunization
  • Immunoglobulin G
  • Immunoglobulin M
  • Male
  • Neoplasm Recurrence, Local
  • Prospective Studies
  • Prostate
  • Prostate-Specific Antigen
  • Prostatic Neoplasms* / therapy
  • Testosterone
  • Vaccination
  • Vaccines*

Substances

  • Gonadotropin-Releasing Hormone
  • Prostate-Specific Antigen
  • Immunoglobulin G
  • Vaccines
  • Testosterone
  • Immunoglobulin M