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Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin
BACKGROUND: Intratumoral BCG therapy, one of the earliest immunotherapies, can lead to infiltration of immune cells into a treated tumor. However, an increase in the number of BCG-induced tumor-specific T cells in the tumor microenvironment could lead to enhanced therapeutic effects. METHODS: Here,...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286790/ https://www.ncbi.nlm.nih.gov/pubmed/34266884 http://dx.doi.org/10.1136/jitc-2021-002707 |
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author | Ylösmäki, Erkko Fusciello, Manlio Martins, Beatriz Feola, Sara Hamdan, Firas Chiaro, Jacopo Ylösmäki, Leena Vaughan, Matthew J Viitala, Tapani Kulkarni, Prasad S Cerullo, Vincenzo |
author_facet | Ylösmäki, Erkko Fusciello, Manlio Martins, Beatriz Feola, Sara Hamdan, Firas Chiaro, Jacopo Ylösmäki, Leena Vaughan, Matthew J Viitala, Tapani Kulkarni, Prasad S Cerullo, Vincenzo |
author_sort | Ylösmäki, Erkko |
collection | PubMed |
description | BACKGROUND: Intratumoral BCG therapy, one of the earliest immunotherapies, can lead to infiltration of immune cells into a treated tumor. However, an increase in the number of BCG-induced tumor-specific T cells in the tumor microenvironment could lead to enhanced therapeutic effects. METHODS: Here, we have developed a novel cancer vaccine platform based on BCG that can broaden BCG-induced immune responses to include tumor antigens. By physically attaching tumor-specific peptides onto the mycobacterial outer membrane, we were able to induce strong systemic and intratumoral T cell-specific immune responses toward the attached tumor antigens. These therapeutic peptides can be efficiently attached to the mycobacterial outer membrane using a poly-lysine sequence N-terminally fused to the tumor-specific peptides. RESULTS: Using two mouse models of melanoma and a mouse model of colorectal cancer, we observed that the antitumor immune responses of BCG could be improved by coating the BCG with tumor-specific peptides. In addition, by combining this novel cancer vaccine platform with anti-programmed death 1 (anti-PD-1) immune checkpoint inhibitor (ICI) therapy, the number of responders to anti-PD-1 immunotherapy was markedly increased. CONCLUSIONS: This study shows that intratumoral BCG immunotherapy can be improved by coating the bacteria with modified tumor-specific peptides. In addition, this improved BCG immunotherapy can be combined with ICI therapy to obtain enhanced tumor growth control. These results warrant clinical testing of this novel cancer vaccine platform. |
format | Online Article Text |
id | pubmed-8286790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-82867902021-07-30 Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin Ylösmäki, Erkko Fusciello, Manlio Martins, Beatriz Feola, Sara Hamdan, Firas Chiaro, Jacopo Ylösmäki, Leena Vaughan, Matthew J Viitala, Tapani Kulkarni, Prasad S Cerullo, Vincenzo J Immunother Cancer Oncolytic and Local Immunotherapy BACKGROUND: Intratumoral BCG therapy, one of the earliest immunotherapies, can lead to infiltration of immune cells into a treated tumor. However, an increase in the number of BCG-induced tumor-specific T cells in the tumor microenvironment could lead to enhanced therapeutic effects. METHODS: Here, we have developed a novel cancer vaccine platform based on BCG that can broaden BCG-induced immune responses to include tumor antigens. By physically attaching tumor-specific peptides onto the mycobacterial outer membrane, we were able to induce strong systemic and intratumoral T cell-specific immune responses toward the attached tumor antigens. These therapeutic peptides can be efficiently attached to the mycobacterial outer membrane using a poly-lysine sequence N-terminally fused to the tumor-specific peptides. RESULTS: Using two mouse models of melanoma and a mouse model of colorectal cancer, we observed that the antitumor immune responses of BCG could be improved by coating the BCG with tumor-specific peptides. In addition, by combining this novel cancer vaccine platform with anti-programmed death 1 (anti-PD-1) immune checkpoint inhibitor (ICI) therapy, the number of responders to anti-PD-1 immunotherapy was markedly increased. CONCLUSIONS: This study shows that intratumoral BCG immunotherapy can be improved by coating the bacteria with modified tumor-specific peptides. In addition, this improved BCG immunotherapy can be combined with ICI therapy to obtain enhanced tumor growth control. These results warrant clinical testing of this novel cancer vaccine platform. BMJ Publishing Group 2021-07-15 /pmc/articles/PMC8286790/ /pubmed/34266884 http://dx.doi.org/10.1136/jitc-2021-002707 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Oncolytic and Local Immunotherapy Ylösmäki, Erkko Fusciello, Manlio Martins, Beatriz Feola, Sara Hamdan, Firas Chiaro, Jacopo Ylösmäki, Leena Vaughan, Matthew J Viitala, Tapani Kulkarni, Prasad S Cerullo, Vincenzo Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin |
title | Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin |
title_full | Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin |
title_fullStr | Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin |
title_full_unstemmed | Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin |
title_short | Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin |
title_sort | novel personalized cancer vaccine platform based on bacillus calmette-guèrin |
topic | Oncolytic and Local Immunotherapy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286790/ https://www.ncbi.nlm.nih.gov/pubmed/34266884 http://dx.doi.org/10.1136/jitc-2021-002707 |
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