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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,...

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Autores principales: Ylösmäki, Erkko, Fusciello, Manlio, Martins, Beatriz, Feola, Sara, Hamdan, Firas, Chiaro, Jacopo, Ylösmäki, Leena, Vaughan, Matthew J, Viitala, Tapani, Kulkarni, Prasad S, Cerullo, Vincenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
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.
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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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