Recombinant single-cycle influenza virus with exchangeable pseudotypes allows repeated immunization to augment anti-tumour immunity with immune checkpoint inhibitors
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 a...
Main Authors: | , , , , , , , , , |
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eLife Sciences Publications Ltd
2023-01-01
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Online Access: | https://elifesciences.org/articles/76414 |
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author | Matheswaran Kandasamy Uzi Gileadi Pramila Rijal Tiong Kit Tan Lian N Lee Jili Chen Gennaro Prota Paul Klenerman Alain Townsend Vincenzo Cerundolo |
author_facet | Matheswaran Kandasamy Uzi Gileadi Pramila Rijal Tiong Kit Tan Lian N Lee Jili Chen Gennaro Prota Paul Klenerman Alain Townsend Vincenzo Cerundolo |
author_sort | Matheswaran Kandasamy |
collection | DOAJ |
description | 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 (NY-ESO-1 S-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. |
first_indexed | 2024-04-10T23:52:05Z |
format | Article |
id | doaj.art-19381c4da57642bb86445baca9176ae3 |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-10T23:52:05Z |
publishDate | 2023-01-01 |
publisher | eLife Sciences Publications Ltd |
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series | eLife |
spelling | doaj.art-19381c4da57642bb86445baca9176ae32023-01-10T16:35:18ZengeLife Sciences Publications LtdeLife2050-084X2023-01-011210.7554/eLife.76414Recombinant single-cycle influenza virus with exchangeable pseudotypes allows repeated immunization to augment anti-tumour immunity with immune checkpoint inhibitorsMatheswaran Kandasamy0https://orcid.org/0000-0001-7734-4600Uzi Gileadi1https://orcid.org/0000-0001-7348-9204Pramila Rijal2Tiong Kit Tan3Lian N Lee4Jili Chen5Gennaro Prota6Paul Klenerman7Alain Townsend8Vincenzo Cerundolo9MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomNuffield Department of Medicine and Translational Gastroenterology Unit, Peter Medawar Building, University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomNuffield Department of Medicine and Translational Gastroenterology Unit, Peter Medawar Building, University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomVirus-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 (NY-ESO-1 S-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.https://elifesciences.org/articles/76414cancer vaccineinfluenza virustumour metastasis |
spellingShingle | Matheswaran Kandasamy Uzi Gileadi Pramila Rijal Tiong Kit Tan Lian N Lee Jili Chen Gennaro Prota Paul Klenerman Alain Townsend Vincenzo Cerundolo Recombinant single-cycle influenza virus with exchangeable pseudotypes allows repeated immunization to augment anti-tumour immunity with immune checkpoint inhibitors eLife cancer vaccine influenza virus tumour metastasis |
title | Recombinant single-cycle influenza virus with exchangeable pseudotypes allows repeated immunization to augment anti-tumour immunity with immune checkpoint inhibitors |
title_full | Recombinant single-cycle influenza virus with exchangeable pseudotypes allows repeated immunization to augment anti-tumour immunity with immune checkpoint inhibitors |
title_fullStr | Recombinant single-cycle influenza virus with exchangeable pseudotypes allows repeated immunization to augment anti-tumour immunity with immune checkpoint inhibitors |
title_full_unstemmed | Recombinant single-cycle influenza virus with exchangeable pseudotypes allows repeated immunization to augment anti-tumour immunity with immune checkpoint inhibitors |
title_short | Recombinant single-cycle influenza virus with exchangeable pseudotypes allows repeated immunization to augment anti-tumour immunity with immune checkpoint inhibitors |
title_sort | recombinant single cycle influenza virus with exchangeable pseudotypes allows repeated immunization to augment anti tumour immunity with immune checkpoint inhibitors |
topic | cancer vaccine influenza virus tumour metastasis |
url | https://elifesciences.org/articles/76414 |
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