2023 World Conference on Lung Cancer (Posters)-P1.08. Hyper-Interferon Sensitive Influenza Virus Induces Immune Activation and Overcomes Resistance to Anti-PD-1 in Murine NSCLC

P1.08. Hyper-Interferon Sensitive Influenza Virus Induces Immune Activation and Overcomes Resistance to Anti-PD-1 in Murine NSCLC - PDF(Slides)

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A recent study conducted by researchers from the David Geffen School of Medicine at UCLA and the Department of Molecular and Medical Pharmacology has shown that a novel attenuated viral vaccine called Hyper-Interferon Sensitive (HIS) virus, when used in combination with anti-PD-1 therapy, can overcome resistance to treatment in murine non-small cell lung cancer (NSCLC). The researchers hypothesized that intranasal HIS vaccination could enhance T cell priming and activation, thus sensitizing non-responsive NSCLC tumors to anti-PD-1 therapy.<br /><br />The study found that intranasal HIS vaccination in mice resulted in strong induction of host interferon-I (IFN-I), leading to a decrease in viral replication and spreading. Additionally, HIS vaccination combined with anti-PD-1 therapy promoted Th1 polarization and the infiltration of polyfunctional cytotoxic T cells into the tumor microenvironment (TME).<br /><br />The researchers also demonstrated that HIS virotherapy was safe in immunocompetent mice and effectively inhibited NSCLC tumor growth. Furthermore, combination therapy with HIS and anti-PD-1 generated systemic tumor-specific immune memory.<br /><br />The efficacy of HIS virotherapy was found to be dependent on the induction of host IFN-I. Mutational burden analysis showed that the Kras-mutant murine NSCLC cells used in the study had an increased tumor mutational burden, similar to human lung adenocarcinoma tumors.<br /><br />Overall, this study highlights the potential of HIS vaccination combined with anti-PD-1 therapy as a promising treatment strategy for NSCLC patients who are resistant to current immune checkpoint inhibitors.

Asset Subtitle

Ramin Salehi-rad

Meta Tag

Speaker Ramin Salehi-rad

Topic Tumor Biology: Translational Biology - Drug Resistance

Keywords

attenuated viral vaccine

Hyper-Interferon Sensitive virus

anti-PD-1 therapy

resistance to treatment

murine non-small cell lung cancer

intranasal HIS vaccination

T cell priming

tumor microenvironment

Th1 polarization

cytotoxic T cells