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TNFa and IL2 Encoding Oncolytic Adenovirus Activates Pathogen and Danger-Associated Immunological Signaling

Camilla Heiniö1, Riikka Havunen2, Joao Santos1,2

  • 1Cancer Gene Therapy Group, Faculty of Medicine, TRIMM, University of Helsinki, Haartmaninkatu 3, 00290 Helsinki, Finland.

Cells
|April 1, 2020
PubMed

Insights

This study reveals that a novel oncolytic adenovirus, OAd.TNFa-IL2, activates the AIM2 inflammasome. This activation enhances the anti-tumor immune response, offering a new strategy to overcome tumor resistance.

Area of Science:

  • Immunology
  • Virology
  • Oncology

Background:

  • Tumor resistance to traditional treatments necessitates novel therapeutic strategies.
  • Oncolytic viruses are engineered to selectively infect and kill cancer cells.
  • Pattern recognition receptors (PRRs) mediate cellular responses to viral infections, influencing treatment outcomes.

Purpose of the Study:

  • To investigate the effects of the cytokine-armed oncolytic adenovirus OAd.TNFa-IL2 on PRR-mediated signaling.
  • To determine which PRRs are crucial for mediating an anti-tumor response to OAd.TNFa-IL2 virotherapy.
  • To understand how OAd.TNFa-IL2 modulates the tumor microenvironment through PRR activation.

Main Methods:

  • Treatment of tumor models with OAd.TNFa-IL2 (TILT-123).
  • Analysis of danger-associated molecular pattern (DAMP) and pathogen-associated molecular pattern (PAMP) release.
  • Assessment of PRR activation, specifically the AIM2 inflammasome.
  • Evaluation of tumor microenvironment changes and anti-tumor immune responses.

Main Results:

  • OAd.TNFa-IL2 infection induced significant DAMP and PAMP release.
  • The AIM2 inflammasome was demonstrably activated following OAd.TNFa-IL2 treatment.
  • This activation led to a modulation of the tumor microenvironment, creating an immunostimulatory milieu.
  • PRR signaling was identified as a key mediator of the anti-tumor effects.

Conclusions:

  • OAd.TNFa-IL2 effectively breaks tumor resistance by activating PRR-mediated pathways.
  • AIM2 inflammasome activation is a critical mechanism driving the anti-tumor immune response in OAd.TNFa-IL2 virotherapy.
  • Targeting PRR signaling presents a promising avenue for optimizing oncolytic virus therapy.
Keywords:
AIM2DAMPPAMPTILT-123aenovirusimmunological cell deathimmunotherapyoncolytic virusvirotherapy

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