Modulation of the tumor microenvironment with an oncolytic adenovirus for effective T-cell therapy and checkpoint

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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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João Manuel Santos1, Riikka Havunen1, Akseli Hemminki2

  • 1Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Ltd, Helsinki, Finland.

Methods in Enzymology
|March 4, 2020
PubMed

Insights

Oncolytic adenoviruses offer a promising solution to overcome tumor microenvironment challenges and improve cancer immunotherapy. They enhance adoptive T-cell transfer and checkpoint blockade efficacy for solid tumors.

Area of Science:

  • Immunology
  • Oncology
  • Virology

Background:

  • Solid tumors present significant challenges to current immunotherapies like adoptive T-cell transfer and checkpoint blockade.
  • Limited clinical benefits are observed in patients with advanced or metastatic solid malignancies due to the tumor microenvironment.
  • Existing treatments often involve toxic regimens or suffer from low response rates.

Purpose of the Study:

  • To provide an overview of tumor microenvironmental challenges in solid tumors.
  • To explain how oncolytic adenoviruses can counteract these barriers.
  • To discuss the immunotherapeutic potential of oncolytic adenoviruses in combination with existing therapies.

Main Methods:

  • Review of existing literature on tumor microenvironment.
  • Analysis of oncolytic adenovirus properties and mechanisms.
  • Discussion of clinical experiences with adoptive T-cell therapy and immune checkpoint inhibitors.

Main Results:

  • Oncolytic adenoviruses possess intrinsic modulatory effects on the intratumoral immune compartment.
  • They offer engineering capabilities and a favorable safety profile for combination therapy.
  • Oncolytic adenoviruses can potentially overcome limitations of current immunotherapies.

Conclusions:

  • Oncolytic adenoviruses represent an attractive strategy to enhance cancer immunotherapy.
  • Combination therapy involving oncolytic adenoviruses may improve outcomes for solid tumors.
  • Further clinical investigation is warranted to fully realize their immunotherapeutic potential.
Keywords:
AdenovirusAdoptive T-cell therapyCAR-T cellsCheckpoint inhibitionClinical trialsImmunotherapyOncolytic virusT-cell receptor (TCR)-engineered T cellsTumor microenvironmentTumor-infiltrating lymphocytes

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