Cargando…

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

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 re...

Descripción completa

Detalles Bibliográficos
Autores principales: Campal-Espinosa, Ana Cristina, Junco-Barranco, Jesús Arturo, Fuentes-Aguilar, Franklin, Calzada-Aguilera, Lesvia, Rivacoba-Betancourt, Annia, Rodríguez-Bueno, Ranfis Humberto, Bover-Campal, Ana Claudia, Bover-Fuentes, Eddy Emilio, González, Lourdes, de Quesada, Lourdes, Alvarez, Allelin, Garay-Pérez, Hilda Elisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576932/
https://www.ncbi.nlm.nih.gov/pubmed/37828833
http://dx.doi.org/10.1177/15330338231207318
_version_ 1785121221914918912
author Campal-Espinosa, Ana Cristina
Junco-Barranco, Jesús Arturo
Fuentes-Aguilar, Franklin
Calzada-Aguilera, Lesvia
Rivacoba-Betancourt, Annia
Rodríguez-Bueno, Ranfis Humberto
Bover-Campal, Ana Claudia
Bover-Fuentes, Eddy Emilio
González, Lourdes
de Quesada, Lourdes
Alvarez, Allelin
Garay-Pérez, Hilda Elisa
author_facet Campal-Espinosa, Ana Cristina
Junco-Barranco, Jesús Arturo
Fuentes-Aguilar, Franklin
Calzada-Aguilera, Lesvia
Rivacoba-Betancourt, Annia
Rodríguez-Bueno, Ranfis Humberto
Bover-Campal, Ana Claudia
Bover-Fuentes, Eddy Emilio
González, Lourdes
de Quesada, Lourdes
Alvarez, Allelin
Garay-Pérez, Hilda Elisa
author_sort Campal-Espinosa, Ana Cristina
collection PubMed
description 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.
format Online
Article
Text
id pubmed-10576932
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher SAGE Publications
record_format MEDLINE/PubMed
spelling pubmed-105769322023-10-16 Influence of Humoral Response Against GnRH, Generated by Immunization with a Therapeutic Vaccine Candidate on the Evolution of Patients with Castration-Sensitive Prostate Adenocarcinoma Campal-Espinosa, Ana Cristina Junco-Barranco, Jesús Arturo Fuentes-Aguilar, Franklin Calzada-Aguilera, Lesvia Rivacoba-Betancourt, Annia Rodríguez-Bueno, Ranfis Humberto Bover-Campal, Ana Claudia Bover-Fuentes, Eddy Emilio González, Lourdes de Quesada, Lourdes Alvarez, Allelin Garay-Pérez, Hilda Elisa Technol Cancer Res Treat Vaccines for cancer immunotherapy 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. SAGE Publications 2023-10-13 /pmc/articles/PMC10576932/ /pubmed/37828833 http://dx.doi.org/10.1177/15330338231207318 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Vaccines for cancer immunotherapy
Campal-Espinosa, Ana Cristina
Junco-Barranco, Jesús Arturo
Fuentes-Aguilar, Franklin
Calzada-Aguilera, Lesvia
Rivacoba-Betancourt, Annia
Rodríguez-Bueno, Ranfis Humberto
Bover-Campal, Ana Claudia
Bover-Fuentes, Eddy Emilio
González, Lourdes
de Quesada, Lourdes
Alvarez, Allelin
Garay-Pérez, Hilda Elisa
Influence of Humoral Response Against GnRH, Generated by Immunization with a Therapeutic Vaccine Candidate on the Evolution of Patients with Castration-Sensitive Prostate Adenocarcinoma
title Influence of Humoral Response Against GnRH, Generated by Immunization with a Therapeutic Vaccine Candidate on the Evolution of Patients with Castration-Sensitive Prostate Adenocarcinoma
title_full Influence of Humoral Response Against GnRH, Generated by Immunization with a Therapeutic Vaccine Candidate on the Evolution of Patients with Castration-Sensitive Prostate Adenocarcinoma
title_fullStr Influence of Humoral Response Against GnRH, Generated by Immunization with a Therapeutic Vaccine Candidate on the Evolution of Patients with Castration-Sensitive Prostate Adenocarcinoma
title_full_unstemmed Influence of Humoral Response Against GnRH, Generated by Immunization with a Therapeutic Vaccine Candidate on the Evolution of Patients with Castration-Sensitive Prostate Adenocarcinoma
title_short Influence of Humoral Response Against GnRH, Generated by Immunization with a Therapeutic Vaccine Candidate on the Evolution of Patients with Castration-Sensitive Prostate Adenocarcinoma
title_sort influence of humoral response against gnrh, generated by immunization with a therapeutic vaccine candidate on the evolution of patients with castration-sensitive prostate adenocarcinoma
topic Vaccines for cancer immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576932/
https://www.ncbi.nlm.nih.gov/pubmed/37828833
http://dx.doi.org/10.1177/15330338231207318
work_keys_str_mv AT campalespinosaanacristina influenceofhumoralresponseagainstgnrhgeneratedbyimmunizationwithatherapeuticvaccinecandidateontheevolutionofpatientswithcastrationsensitiveprostateadenocarcinoma
AT juncobarrancojesusarturo influenceofhumoralresponseagainstgnrhgeneratedbyimmunizationwithatherapeuticvaccinecandidateontheevolutionofpatientswithcastrationsensitiveprostateadenocarcinoma
AT fuentesaguilarfranklin influenceofhumoralresponseagainstgnrhgeneratedbyimmunizationwithatherapeuticvaccinecandidateontheevolutionofpatientswithcastrationsensitiveprostateadenocarcinoma
AT calzadaaguileralesvia influenceofhumoralresponseagainstgnrhgeneratedbyimmunizationwithatherapeuticvaccinecandidateontheevolutionofpatientswithcastrationsensitiveprostateadenocarcinoma
AT rivacobabetancourtannia influenceofhumoralresponseagainstgnrhgeneratedbyimmunizationwithatherapeuticvaccinecandidateontheevolutionofpatientswithcastrationsensitiveprostateadenocarcinoma
AT rodriguezbuenoranfishumberto influenceofhumoralresponseagainstgnrhgeneratedbyimmunizationwithatherapeuticvaccinecandidateontheevolutionofpatientswithcastrationsensitiveprostateadenocarcinoma
AT bovercampalanaclaudia influenceofhumoralresponseagainstgnrhgeneratedbyimmunizationwithatherapeuticvaccinecandidateontheevolutionofpatientswithcastrationsensitiveprostateadenocarcinoma
AT boverfuenteseddyemilio influenceofhumoralresponseagainstgnrhgeneratedbyimmunizationwithatherapeuticvaccinecandidateontheevolutionofpatientswithcastrationsensitiveprostateadenocarcinoma
AT gonzalezlourdes influenceofhumoralresponseagainstgnrhgeneratedbyimmunizationwithatherapeuticvaccinecandidateontheevolutionofpatientswithcastrationsensitiveprostateadenocarcinoma
AT dequesadalourdes influenceofhumoralresponseagainstgnrhgeneratedbyimmunizationwithatherapeuticvaccinecandidateontheevolutionofpatientswithcastrationsensitiveprostateadenocarcinoma
AT alvarezallelin influenceofhumoralresponseagainstgnrhgeneratedbyimmunizationwithatherapeuticvaccinecandidateontheevolutionofpatientswithcastrationsensitiveprostateadenocarcinoma
AT garayperezhildaelisa influenceofhumoralresponseagainstgnrhgeneratedbyimmunizationwithatherapeuticvaccinecandidateontheevolutionofpatientswithcastrationsensitiveprostateadenocarcinoma