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Telomerase-based GX301 cancer vaccine in patients with metastatic castration-resistant prostate cancer: a randomized phase II trial
Debate is around the optimal immunization regimen for cancer vaccines since too intense vaccination schedules may exhaust reactive lymphocytes. GX301 is a telomerase-based cancer vaccine whose safety and immunological effects were tested in a phase I trial applying an eight administrations schedule....
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571235/ https://www.ncbi.nlm.nih.gov/pubmed/34351436 http://dx.doi.org/10.1007/s00262-021-03024-0 |
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author | Filaci, Gilberto Fenoglio, Daniela Nolè, Franco Zanardi, Elisa Tomasello, Laura Aglietta, Massimo Del Conte, Gianluca Carles, Joan Morales-Barrera, Rafael Guglielmini, Pamela Scagliotti, Giorgio Signori, Alessio Parodi, Alessia Kalli, Francesca Astone, Giuseppina Ferrera, Francesca Altosole, Tiziana Lamperti, Giuseppina Criscuolo, Domenico Gianese, Francesco Boccardo, Francesco |
author_facet | Filaci, Gilberto Fenoglio, Daniela Nolè, Franco Zanardi, Elisa Tomasello, Laura Aglietta, Massimo Del Conte, Gianluca Carles, Joan Morales-Barrera, Rafael Guglielmini, Pamela Scagliotti, Giorgio Signori, Alessio Parodi, Alessia Kalli, Francesca Astone, Giuseppina Ferrera, Francesca Altosole, Tiziana Lamperti, Giuseppina Criscuolo, Domenico Gianese, Francesco Boccardo, Francesco |
author_sort | Filaci, Gilberto |
collection | PubMed |
description | Debate is around the optimal immunization regimen for cancer vaccines since too intense vaccination schedules may exhaust reactive lymphocytes. GX301 is a telomerase-based cancer vaccine whose safety and immunological effects were tested in a phase I trial applying an eight administrations schedule. Main objective of this study was to comparatively analyse safety and immunological response to three GX301 regimens in metastatic castration-resistant prostate cancer patients with response/disease stability after docetaxel chemotherapy. This was a multicentre, randomized, parallel-group, open-label trial registered with EudraCT (2014-000095-26) and ClinicalTrials.gov (NCT02293707, 2014). Ninety-eight patients were randomized to receive either eight (regimen 1), four (regimen 2) or two (regimen 3) vaccine administrations. Sixty-three patients were assessable for the primary immunological end-point. Vaccine-specific immune responses were evaluated by intracellular staining for IFN, elispot and cytotoxic assay at 90 and 180 days from baseline. No major side effects were recorded. A 54% overall immune responder rate was observed with 95% of patients showing at least one vaccine-specific immune response. Rate of immunological responders and number of immunizations were proportionally related, suggesting superiority of regimens 1 and 2 over regimen 3. Overall survival did not differ among regimens in both immunological responders and non-responders and was inversely associated (P = 0.002) with increase in the number of circulating CD8 + T regulatory cells at 180 days. These data indicate that GX301 cancer vaccine is safe and immunogenic in metastatic castration-resistant prostate cancer patients. Schedules with high number of administrations should be preferred in future studies due to their better immunological outcome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-021-03024-0. |
format | Online Article Text |
id | pubmed-8571235 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-85712352021-11-08 Telomerase-based GX301 cancer vaccine in patients with metastatic castration-resistant prostate cancer: a randomized phase II trial Filaci, Gilberto Fenoglio, Daniela Nolè, Franco Zanardi, Elisa Tomasello, Laura Aglietta, Massimo Del Conte, Gianluca Carles, Joan Morales-Barrera, Rafael Guglielmini, Pamela Scagliotti, Giorgio Signori, Alessio Parodi, Alessia Kalli, Francesca Astone, Giuseppina Ferrera, Francesca Altosole, Tiziana Lamperti, Giuseppina Criscuolo, Domenico Gianese, Francesco Boccardo, Francesco Cancer Immunol Immunother Clinical Trial Report Debate is around the optimal immunization regimen for cancer vaccines since too intense vaccination schedules may exhaust reactive lymphocytes. GX301 is a telomerase-based cancer vaccine whose safety and immunological effects were tested in a phase I trial applying an eight administrations schedule. Main objective of this study was to comparatively analyse safety and immunological response to three GX301 regimens in metastatic castration-resistant prostate cancer patients with response/disease stability after docetaxel chemotherapy. This was a multicentre, randomized, parallel-group, open-label trial registered with EudraCT (2014-000095-26) and ClinicalTrials.gov (NCT02293707, 2014). Ninety-eight patients were randomized to receive either eight (regimen 1), four (regimen 2) or two (regimen 3) vaccine administrations. Sixty-three patients were assessable for the primary immunological end-point. Vaccine-specific immune responses were evaluated by intracellular staining for IFN, elispot and cytotoxic assay at 90 and 180 days from baseline. No major side effects were recorded. A 54% overall immune responder rate was observed with 95% of patients showing at least one vaccine-specific immune response. Rate of immunological responders and number of immunizations were proportionally related, suggesting superiority of regimens 1 and 2 over regimen 3. Overall survival did not differ among regimens in both immunological responders and non-responders and was inversely associated (P = 0.002) with increase in the number of circulating CD8 + T regulatory cells at 180 days. These data indicate that GX301 cancer vaccine is safe and immunogenic in metastatic castration-resistant prostate cancer patients. Schedules with high number of administrations should be preferred in future studies due to their better immunological outcome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-021-03024-0. Springer Berlin Heidelberg 2021-08-05 2021 /pmc/articles/PMC8571235/ /pubmed/34351436 http://dx.doi.org/10.1007/s00262-021-03024-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Clinical Trial Report Filaci, Gilberto Fenoglio, Daniela Nolè, Franco Zanardi, Elisa Tomasello, Laura Aglietta, Massimo Del Conte, Gianluca Carles, Joan Morales-Barrera, Rafael Guglielmini, Pamela Scagliotti, Giorgio Signori, Alessio Parodi, Alessia Kalli, Francesca Astone, Giuseppina Ferrera, Francesca Altosole, Tiziana Lamperti, Giuseppina Criscuolo, Domenico Gianese, Francesco Boccardo, Francesco Telomerase-based GX301 cancer vaccine in patients with metastatic castration-resistant prostate cancer: a randomized phase II trial |
title | Telomerase-based GX301 cancer vaccine in patients with metastatic castration-resistant prostate cancer: a randomized phase II trial |
title_full | Telomerase-based GX301 cancer vaccine in patients with metastatic castration-resistant prostate cancer: a randomized phase II trial |
title_fullStr | Telomerase-based GX301 cancer vaccine in patients with metastatic castration-resistant prostate cancer: a randomized phase II trial |
title_full_unstemmed | Telomerase-based GX301 cancer vaccine in patients with metastatic castration-resistant prostate cancer: a randomized phase II trial |
title_short | Telomerase-based GX301 cancer vaccine in patients with metastatic castration-resistant prostate cancer: a randomized phase II trial |
title_sort | telomerase-based gx301 cancer vaccine in patients with metastatic castration-resistant prostate cancer: a randomized phase ii trial |
topic | Clinical Trial Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571235/ https://www.ncbi.nlm.nih.gov/pubmed/34351436 http://dx.doi.org/10.1007/s00262-021-03024-0 |
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