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Updated: Jul 9, 2025

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo

Published on: January 7, 2019

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Oncolytic adenoviruses expressing checkpoint inhibitors for cancer therapy

Daoyuan Xie1, Yaomei Tian1,2, Die Hu1

  • 1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.

Signal Transduction and Targeted Therapy
|November 28, 2023
PubMed

Insights

Engineered oncolytic viruses (OVs) delivering immune checkpoint inhibitors (ICIs) can overcome tumor resistance. Tailored OVs targeting specific tumor microenvironments (TME) demonstrated potent, long-term antitumor immunity and memory.

Area of Science:

  • Oncology
  • Immunotherapy
  • Virology

Background:

  • Immune checkpoint inhibitors (ICIs) show limited efficacy due to tumor microenvironment (TME) resistance.
  • Oncolytic viruses (OVs) can modulate the TME and enhance systemic antitumor immunity.
  • Tailoring therapies to tumor-specific immune landscapes is crucial for effective cancer treatment.

Purpose of the Study:

  • To engineer novel oncolytic adenoviruses (OAds) armed with ICIs to overcome TME-mediated resistance.
  • To investigate the efficacy of OAds expressing SIRPα-Fc, Siglec10-Fc, and TIGIT-Fc against tumors with diverse immune cell compositions.
  • To evaluate the potential of OAds in combination with existing immunotherapies.

Main Methods:

  • Generation of three recombinant OAds: OAd-SIRPα-Fc, OAd-Siglec10-Fc, and OAd-TIGIT-Fc.
  • In vivo assessment of OAd efficacy in tumor suppression and immune response modulation.
  • Evaluation of combination therapy with anti-PD-1 in a 4T1 tumor model.

Main Results:

  • OAd-SIRPα-Fc and OAd-Siglec10-Fc demonstrated significant efficacy in macrophage-dominated tumors.
  • OAd-TIGIT-Fc exhibited potent antitumor immunity in CD8+ T-cell-dominated tumors.
  • Recombinant OAds induced inflammatory responses, generated long-term antitumor memory, and combination therapy enhanced efficacy.

Conclusions:

  • Rationally designed OAds expressing ICIs can be tailored to specific TME immune landscapes for precise cancer immunotherapy.
  • Engineered OVs offer a promising strategy to enhance ICI efficacy and overcome treatment resistance.
  • Targeted OV-based immunotherapies hold potential for durable antitumor responses and long-term cancer control.

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