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Recombinant single-cycle influenza virus as a new tool to augment antitumour immunity with immune checkpoint inhibitors

View ORCID ProfileMatheswaran Kandasamy, Uzi Gileadi, Pramila Rijal, Tiong Kit Tan, Lian Ni Lee, Jili Chen, Gennaro Prota, Jing Zhang, Terence Rabbitts, Alain Townsend, Vincenzo Cerundolo
doi: https://doi.org/10.1101/2021.07.31.454512
Matheswaran Kandasamy
1MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, UK
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  • ORCID record for Matheswaran Kandasamy
  • For correspondence: [email protected]
Uzi Gileadi
1MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, UK
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Pramila Rijal
1MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, UK
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Tiong Kit Tan
1MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, UK
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Lian Ni Lee
3Nuffield Department of Medicine and Translational Gastroenterology Unit, Peter Medawar Building, University of Oxford, Oxford, United Kingdom
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Jili Chen
1MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, UK
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Gennaro Prota
1MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, UK
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Jing Zhang
2MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, UK
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Terence Rabbitts
2MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, UK
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Alain Townsend
1MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, UK
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Vincenzo Cerundolo
1MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, UK
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Abstract

Virus-based tumour vaccines offer many advantages compared to other antigen delivering systems. They generate concerted innate and adaptive immune response, and robust CD8+T cell responses. We engineered a non-replicating pseudotyped influenza virus (S-FLU) to deliver the well-known cancer testis antigen, NY-ESO-1 (S-NY-ESO-1 FLU). Intranasal or intramuscular immunization of NY-ESO-1 S-FLU virus in mice elicited a strong NY-ESO-1 specific CD8+T cell response in lungs and spleen that resulted in the regression of NY-ESO-1 expressing lung tumour and subcutaneous tumour respectively. Combined administration with anti PD-1 antibody, NY-ESO-1 S-FLU virus augmented the tumour protection by reducing the tumour metastasis. We propose that the antigen delivery through S-FLU is highly efficient in inducing antigen specific CD8+T cell response and protection against tumour development in combination with PD-1 blockade.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Disclosure of Potential Conflicts of Interest: All authors report no potential conflicts of interest

  • Authors’ Contributions: MK, UG, AT and VC designed the study and MK, PR, TT, LL performed experiments. MK analysed the data and wrote the manuscript. MK, UG, PR, TT, LL, GP and AT edited the manuscript. All authors discussed the results, commented on the manuscript, and agreed on publication

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted August 01, 2021.
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Recombinant single-cycle influenza virus as a new tool to augment antitumour immunity with immune checkpoint inhibitors
Matheswaran Kandasamy, Uzi Gileadi, Pramila Rijal, Tiong Kit Tan, Lian Ni Lee, Jili Chen, Gennaro Prota, Jing Zhang, Terence Rabbitts, Alain Townsend, Vincenzo Cerundolo
bioRxiv 2021.07.31.454512; doi: https://doi.org/10.1101/2021.07.31.454512
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Recombinant single-cycle influenza virus as a new tool to augment antitumour immunity with immune checkpoint inhibitors
Matheswaran Kandasamy, Uzi Gileadi, Pramila Rijal, Tiong Kit Tan, Lian Ni Lee, Jili Chen, Gennaro Prota, Jing Zhang, Terence Rabbitts, Alain Townsend, Vincenzo Cerundolo
bioRxiv 2021.07.31.454512; doi: https://doi.org/10.1101/2021.07.31.454512

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