Novel personalized cancer vaccine platform based on Bacillus Calmette-Guerin

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http://hdl.handle.net/10138/334461

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Ylösmäki , E , Fusciello , M , Martins , B , Feola , S , Hamdan , F , Chiaro , J , Ylösmäki , L , Vaughan , M J , Viitala , T , Kulkarni , P S & Cerullo , V 2021 , ' Novel personalized cancer vaccine platform based on Bacillus Calmette-Guerin ' , Journal for Immunotherapy of Cancer , vol. 9 , no. 7 , 002707 . https://doi.org/10.1136/jitc-2021-002707

Titel: Novel personalized cancer vaccine platform based on Bacillus Calmette-Guerin
Författare: Ylösmäki, Erkko; Fusciello, Manlio; Martins, Beatriz; Feola, Sara; Hamdan, Firas; Chiaro, Jacopo; Ylösmäki, Leena; Vaughan, Matthew J.; Viitala, Tapani; Kulkarni, Prasad S.; Cerullo, Vincenzo
Upphovmannens organisation: ImmunoViroTherapy Lab
Division of Pharmaceutical Biosciences
Drug Research Program
TRIMM - Translational Immunology Research Program
Division of Pharmaceutical Chemistry and Technology
Pharmaceutical biophysics group
Digital Precision Cancer Medicine (iCAN)
Datum: 2021
Språk: eng
Sidantal: 13
Tillhör serie: Journal for Immunotherapy of Cancer
ISSN: 2051-1426
DOI: https://doi.org/10.1136/jitc-2021-002707
Permanenta länken (URI): http://hdl.handle.net/10138/334461
Abstrakt: 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.
Subject: adaptive immunity
immunity
cellular
immunogenicity
vaccine
immunotherapy
active
ADVANCED MELANOMA PATIENTS
MYCOBACTERIUM-BOVIS BCG
PRIME-BOOST VACCINATION
TOPICAL IMIQUIMOD
IMMUNE-RESPONSES
SURFACE-CHARGE
B16 MELANOMA
TUMOR-GROWTH
VIRUS
IMMUNOTHERAPY
3122 Cancers
317 Pharmacy
Referentgranskad: Ja
Licens: cc_by
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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