Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin

Erkko Ylösmäki, Manlio Fusciello, Beatriz Martins, Sara Feola, Firas Hamdan, Jacopo Chiaro, Leena Ylösmäki, Matthew J. Vaughan, Tapani Viitala, Prasad S. Kulkarni, Vincenzo Cerullo*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere002707
JournalJournal for ImmunoTherapy of Cancer
Volume9
Issue number7
DOIs
Publication statusPublished - 15 Jul 2021
Externally publishedYes
MoE publication typeA1 Journal article-refereed

Keywords

  • active
  • adaptive immunity
  • cellular
  • immunity
  • immunogenicity
  • immunotherapy
  • vaccine

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