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Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin

Erkko Ylösmäki, Beatriz Martins, Manlio Fusciello, Sara Feola, Firas Hamdan, Jacopo Chiaro, Leena Ylösmäki, Matthew J. Vaughan, Tapani Viitala, Prasad S. Kulkarni, View ORCID ProfileVincenzo Cerullo
doi: https://doi.org/10.1101/2021.03.05.434062
Erkko Ylösmäki
1Laboratory of Immunovirotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
2TRIMM, Translational Immunology Research Program, University of Helsinki, Finland
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Beatriz Martins
1Laboratory of Immunovirotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
2TRIMM, Translational Immunology Research Program, University of Helsinki, Finland
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Manlio Fusciello
1Laboratory of Immunovirotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
2TRIMM, Translational Immunology Research Program, University of Helsinki, Finland
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Sara Feola
1Laboratory of Immunovirotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
2TRIMM, Translational Immunology Research Program, University of Helsinki, Finland
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Firas Hamdan
1Laboratory of Immunovirotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
2TRIMM, Translational Immunology Research Program, University of Helsinki, Finland
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Jacopo Chiaro
1Laboratory of Immunovirotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
2TRIMM, Translational Immunology Research Program, University of Helsinki, Finland
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Leena Ylösmäki
1Laboratory of Immunovirotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
2TRIMM, Translational Immunology Research Program, University of Helsinki, Finland
3ValoTherapeutics Oy, Helsinki, Finland
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Matthew J. Vaughan
3ValoTherapeutics Oy, Helsinki, Finland
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Tapani Viitala
4Pharmaceutical Biophysics Research Group, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
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Prasad S. Kulkarni
5Serum Institute of India Pvt Ltd, Calcutta, India
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Vincenzo Cerullo
1Laboratory of Immunovirotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
2TRIMM, Translational Immunology Research Program, University of Helsinki, Finland
6iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki
7Department of Molecular Medicine and Medical Biotechnology and CEINGE, Naples University 24 Federico II, 80131, Naples, Italy
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  • ORCID record for Vincenzo Cerullo
  • For correspondence: vincenzo.cerullo@helsinki.fi
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Abstract

Intratumoural bacillus Calmette-Guérin (BCG) therapy, one of the earliest immunotherapies, can lead to infiltration of immune cells into a treated tumour. Here, we have developed a novel cancer vaccine platform based on BCG that can direct BCG-induced immune responses against tumour antigens. By physically attaching tumour-specific peptides onto the mycobacterial outer membrane, we were able to induce strong systemic and intratumoural T cell-specific immune responses towards the attached tumour antigens. These therapeutic peptides can be attached to the mycobacterial outer membrane using a cell-penetrating peptide sequence derived from human immunodeficiency virus Tat, N-terminally fused to the tumour-specific peptides. Alternatively, therapeutic peptides can be conjugated with a poly-lysine sequence N-terminally fused to the tumour-specific peptides. Using two mouse models of melanoma and a mouse model of colorectal cancer, we observed that the anti-tumour responses of BCG can be significantly improved by coating the BCG with tumour-specific peptides. In addition, by combining this novel cancer vaccine platform with anti-PD-1 immune checkpoint inhibitor therapy, the number of responders to anti-PD-1 immunotherapy can be significantly increased.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted March 05, 2021.
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Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin
Erkko Ylösmäki, Beatriz Martins, Manlio Fusciello, Sara Feola, Firas Hamdan, Jacopo Chiaro, Leena Ylösmäki, Matthew J. Vaughan, Tapani Viitala, Prasad S. Kulkarni, Vincenzo Cerullo
bioRxiv 2021.03.05.434062; doi: https://doi.org/10.1101/2021.03.05.434062
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Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin
Erkko Ylösmäki, Beatriz Martins, Manlio Fusciello, Sara Feola, Firas Hamdan, Jacopo Chiaro, Leena Ylösmäki, Matthew J. Vaughan, Tapani Viitala, Prasad S. Kulkarni, Vincenzo Cerullo
bioRxiv 2021.03.05.434062; doi: https://doi.org/10.1101/2021.03.05.434062

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