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Redirecting host preexisting influenza A virus immunity for cancer immunotherapy

We tested the concept that host preexisting influenza A virus immunity can be redirected to inhibit tumor growth and metastasis through systemic administration of influenza A virus–related peptides to targeted tumors. Mice infected with influenza A virus strain A/Puerto Rico/8/34 (PR8) were used as...

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Autores principales: Chaganty, Bharat K. R., Qiu, Songbo, Lu, Yang, Lopez-Berestein, Gabriel, Ozpolat, Bulent, Fan, Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563826/
https://www.ncbi.nlm.nih.gov/pubmed/34731283
http://dx.doi.org/10.1007/s00262-021-03099-9
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author Chaganty, Bharat K. R.
Qiu, Songbo
Lu, Yang
Lopez-Berestein, Gabriel
Ozpolat, Bulent
Fan, Zhen
author_facet Chaganty, Bharat K. R.
Qiu, Songbo
Lu, Yang
Lopez-Berestein, Gabriel
Ozpolat, Bulent
Fan, Zhen
author_sort Chaganty, Bharat K. R.
collection PubMed
description We tested the concept that host preexisting influenza A virus immunity can be redirected to inhibit tumor growth and metastasis through systemic administration of influenza A virus–related peptides to targeted tumors. Mice infected with influenza A virus strain A/Puerto Rico/8/34 (PR8) were used as a model of a host with preexisting viral immunity. The extent to which preexisting influenza A immunity in PR8-immunized mice can be redirected to inhibit tumor growth and metastasis was first examined by ectopic expression of influenza A nucleoprotein (NP) and hemagglutinin (HA) in syngeneic mammary tumor cells via lentiviral transduction. Then, the feasibility of implementing this strategy using a systemic therapy approach was assessed by systemic delivery of major histocompatibility complex class I (MHC-I)-compatible peptides to targeted mammary tumors overexpressing human epidermal growth factor receptor-2 (HER2) in mice using a novel HER2-targeting single-lipid nanoparticle (SLNP). Our results show that preexisting influenza A immunity in PR8-immunized mice could be quickly redirected to syngeneic tumors expressing influenza A NP and HA, leading to strong inhibition of tumor growth and metastasis and improvement of survival compared to the findings in antigen-naïve control mice. MHC-I-compatible peptides could be delivered to targeted mammary tumors in mice using the HER2-targeting SLNP for antigen presentation, which subsequently redirected preexisting influenza A immunity to the tumors to exert antitumor activities. In conclusion, preexisting influenza A immunity can be repurposed for cancer immunotherapy through systemic delivery of influenza A–related peptides to targeted tumors. Further development of the strategy for clinical translation is warranted.
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spelling pubmed-85638262021-11-03 Redirecting host preexisting influenza A virus immunity for cancer immunotherapy Chaganty, Bharat K. R. Qiu, Songbo Lu, Yang Lopez-Berestein, Gabriel Ozpolat, Bulent Fan, Zhen Cancer Immunol Immunother Original Article We tested the concept that host preexisting influenza A virus immunity can be redirected to inhibit tumor growth and metastasis through systemic administration of influenza A virus–related peptides to targeted tumors. Mice infected with influenza A virus strain A/Puerto Rico/8/34 (PR8) were used as a model of a host with preexisting viral immunity. The extent to which preexisting influenza A immunity in PR8-immunized mice can be redirected to inhibit tumor growth and metastasis was first examined by ectopic expression of influenza A nucleoprotein (NP) and hemagglutinin (HA) in syngeneic mammary tumor cells via lentiviral transduction. Then, the feasibility of implementing this strategy using a systemic therapy approach was assessed by systemic delivery of major histocompatibility complex class I (MHC-I)-compatible peptides to targeted mammary tumors overexpressing human epidermal growth factor receptor-2 (HER2) in mice using a novel HER2-targeting single-lipid nanoparticle (SLNP). Our results show that preexisting influenza A immunity in PR8-immunized mice could be quickly redirected to syngeneic tumors expressing influenza A NP and HA, leading to strong inhibition of tumor growth and metastasis and improvement of survival compared to the findings in antigen-naïve control mice. MHC-I-compatible peptides could be delivered to targeted mammary tumors in mice using the HER2-targeting SLNP for antigen presentation, which subsequently redirected preexisting influenza A immunity to the tumors to exert antitumor activities. In conclusion, preexisting influenza A immunity can be repurposed for cancer immunotherapy through systemic delivery of influenza A–related peptides to targeted tumors. Further development of the strategy for clinical translation is warranted. Springer Berlin Heidelberg 2021-11-03 2022 /pmc/articles/PMC8563826/ /pubmed/34731283 http://dx.doi.org/10.1007/s00262-021-03099-9 Text en © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Article
Chaganty, Bharat K. R.
Qiu, Songbo
Lu, Yang
Lopez-Berestein, Gabriel
Ozpolat, Bulent
Fan, Zhen
Redirecting host preexisting influenza A virus immunity for cancer immunotherapy
title Redirecting host preexisting influenza A virus immunity for cancer immunotherapy
title_full Redirecting host preexisting influenza A virus immunity for cancer immunotherapy
title_fullStr Redirecting host preexisting influenza A virus immunity for cancer immunotherapy
title_full_unstemmed Redirecting host preexisting influenza A virus immunity for cancer immunotherapy
title_short Redirecting host preexisting influenza A virus immunity for cancer immunotherapy
title_sort redirecting host preexisting influenza a virus immunity for cancer immunotherapy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563826/
https://www.ncbi.nlm.nih.gov/pubmed/34731283
http://dx.doi.org/10.1007/s00262-021-03099-9
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