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Updated: Jun 16, 2026

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
12:42

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

Published on: January 7, 2019

Carbonic anhydrase modulation in the tumour microenvironment: synergistic pathways with oncolytic viruses in

Reza Zolfaghari Emameh1

  • 1Department of Energy and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

Journal of Drug Targeting
|June 15, 2026
PubMed

Insights

Combining carbonic anhydrase (CA) inhibition with oncolytic viruses (OVs) combats gastrointestinal cancers. This strategy normalizes tumor pH and enhances OV efficacy, leading to improved tumor regression and survival.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunotherapy

Background:

  • Gastrointestinal (GI) malignancies are a major cause of cancer mortality.
  • Acidic tumor microenvironments (TME), regulated by carbonic anhydrase (CA) IX/XII, promote GI cancer progression and therapeutic resistance.
  • Oncolytic viruses (OVs) are promising immunotherapeutics but their efficacy is limited by the acidic TME.

Purpose of the Study:

  • To investigate the synergistic potential of combining CA IX/XII inhibition with OV therapy for GI cancers.
  • To evaluate how this combination impacts the TME and anti-tumor immunity.

Main Methods:

  • Preclinical models of GI cancer were used.
  • The study assessed the effects of combined CA inhibition and OV treatment on tumor pH, invasion, metastasis, and immune responses.

Main Results:

  • CA IX/XII inhibition normalized tumor pH, enhancing OV spread and potency.
  • OV-mediated tumor lysis reduced hypoxia and downregulated CA IX/XII expression.
  • The combination therapy demonstrated enhanced tumor regression, suppressed metastasis, and prolonged survival in preclinical models.

Conclusions:

  • The combination of CA inhibition and OVs offers a synergistic approach to overcome TME-mediated resistance in GI cancers.
  • This multimodal strategy effectively dismantles the metabolic and immunological defenses of the TME.
  • This approach presents a promising translational paradigm for treating GI malignancies.
Keywords:
CA inhibitionOncolytic viruscarbonic anhydrasegastrointestinal malignancyimmunosuppressionmetabolic reprogrammingprecision oncologyvirotherapy

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