Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin

Autor: Vincenzo Cerullo, Matthew J. Vaughan, Tapani Viitala, Firas Hamdan, Leena Ylösmäki, Jacopo Chiaro, Erkko Ylösmäki, Manlio Fusciello, Prasad S. Kulkarni, Sara Feola, Beatriz Martins
Přispěvatelé: 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)
Rok vydání: 2021
Předmět:
Colorectal cancer
medicine.medical_treatment
active
immunogenicity
Mice
0302 clinical medicine
vaccine
TOPICAL IMIQUIMOD
Medicine
Precision Medicine
Peptide sequence
RC254-282
0303 health sciences
biology
IMMUNE-RESPONSES
TUMOR-GROWTH
Melanoma
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
adaptive immunity
3. Good health
317 Pharmacy
PRIME-BOOST VACCINATION
030220 oncology & carcinogenesis
BCG Vaccine
VIRUS
ADVANCED MELANOMA PATIENTS
Female
immunotherapy
3122 Cancers
Bacillus
Cancer Vaccines
03 medical and health sciences
Immune system
Antigen
Cell Line
Tumor
MYCOBACTERIUM-BOVIS BCG
Animals
Humans
030304 developmental biology
business.industry
B16 MELANOMA
Immunotherapy
medicine.disease
biology.organism_classification
immunity
SURFACE-CHARGE
Disease Models
Animal
Oncolytic and Local Immunotherapy
Cancer research
Cancer vaccine
business
cellular
Zdroj: Journal for Immunotherapy of Cancer
Journal for ImmunoTherapy of Cancer, Vol 9, Iss 7 (2021)
DOI: 10.1101/2021.03.05.434062
Popis: 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.
Databáze: OpenAIRE
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