Redirecting Host Preexisting Influenza a Virus Immunity for Cancer Immunotherapy

Authors

Bharat K R Chaganty
Songbo Qiu
Yang Lu
Gabriel Lopez-Berestein
Bulent Ozpolat
Zhen Fan

Publication Date

7-1-2022

Journal

Cancer Immunology, Immunotherapy

Abstract

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.

Keywords

Animals, Antibodies, Viral, Humans, Immunotherapy, Influenza A virus, Influenza, Human, Liposomes, Mice, Mice, Inbred BALB C, Nanoparticles, Neoplasms, Orthomyxoviridae Infections, Peptides, Influenza A virus, Preexisting immunity, Human epidermal growth factor receptor-2, Single-lipid nanoparticle, Cancer immunotherapy

DOI

10.1007/s00262-021-03099-9

PMID

34731283

PMCID

PMC8563826

PubMedCentral® Posted Date

11-3-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes