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Harnessing adenovirus in cancer immunotherapy: evoking cellular immunity and targeting delivery in cell-specific

Miao Zeng1,2, Wei Zhang1,2, Yisheng Li3

  • 1Department of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Hematology Institution of Shenzhen University, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518000, China.

Biomarker Research
|March 26, 2024
PubMed

Insights

Recombinant adenoviruses (rAd), including oncolytic adenoviruses (OAV), show promise as cancer therapeutics. These agents can enhance cancer immunotherapies by remodeling the tumor microenvironment and improving cellular immunity.

Area of Science:

  • Oncolytic virotherapy
  • Cancer immunotherapy
  • Gene therapy

Background:

  • Recombinant adenoviruses (rAd), encompassing replication-competent oncolytic adenoviruses (OAV) and replication-deficient variants, are emerging as significant cancer therapeutics.
  • OAV offer distinct advantages, including selective tumor replication, direct cancer cell killing (oncolysis), and modulation of the tumor microenvironment (TME).

Purpose of the Study:

  • This perspective reviews the development of OAV toolkits and their potential applications in oncology.
  • It explores how rAd can enhance conventional cancer treatments and immunotherapies, such as cancer vaccines and adoptive cell therapy (ACT).
  • The review also examines the strategy of 'hitchhiking' rAd onto immune or stem cells to improve synergistic interactions at tumor sites.

Main Methods:

  • Review of existing literature and preclinical/clinical trial data on rAd and OAV in cancer therapy.
  • Analysis of mechanisms by which rAd exert antitumor effects, including immune cell recruitment and TME reprogramming.
  • Exploration of combination strategies involving rAd with cellular therapies and other cancer treatments.

Main Results:

  • rAd, particularly OAV, demonstrate potential for selective tumor targeting and eradication.
  • rAd can synergize with various cancer immunotherapies, potentially improving treatment efficacy.
  • The 'hitchhiking' approach shows promise for delivering rAd effectively to tumor sites via cellular carriers.
  • rAd have shown utility in addressing challenges like postsurgical residual disease and metastatic tumors.

Conclusions:

  • Recombinant adenoviruses hold significant potential for improving cancer immunotherapy outcomes.
  • Combining rAd with novel immunotherapeutic strategies, including cellular therapies, can enhance antitumor responses.
  • Further research into rAd applications, especially in combination therapies, is warranted to overcome oncological challenges.
Keywords:
Adoptive cell therapyOncolytic adenovirusRecombinant adenovirusTargeted-deliveryTumor immunogenicityTumor microenvironment

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