Redirecting host preexisting influenza A virus immunity for cancer immunotherapy

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1611-1623
Number of pages13
JournalCancer Immunology, Immunotherapy
Volume71
Issue number7
DOIs
StatePublished - Jul 2022

Keywords

  • Cancer immunotherapy
  • Human epidermal growth factor receptor-2
  • Influenza A virus
  • Preexisting immunity
  • Single-lipid nanoparticle

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Redirecting host preexisting influenza A virus immunity for cancer immunotherapy'. Together they form a unique fingerprint.

Cite this