Species D adenoviruses as oncolytics against B-cell cancers

Christopher Y Chen1, Julien S Senac, Eric A Weaver

  • 1Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota 55902, USA.

Abstract

Insights

Species D adenoviruses show unique potential for killing B-cell cancers, unlike other types. These oncolytic viruses could be a new treatment for B-cell malignancies like lymphoma and myeloma.

Area of Science:

  • Virology
  • Oncology
  • Immunology

Background:

  • Oncolytic viruses are anticancer agents that use viral replication to kill cancer cells.
  • Adenovirus serotype 5 (Ad5) is effective against solid tumors but not B-cell cancers due to low coxsackie and adenoviral receptor (CAR) expression.
  • Investigating alternative adenoviruses is crucial for expanding oncolytic virotherapy to B-cell malignancies.

Purpose of the Study:

  • To identify adenoviruses with enhanced potency against B-cell cancers.
  • To explore the adenovirus virome for novel oncolytic agents targeting B-cell malignancies.

Main Methods:

  • In vitro testing of 15 adenoviruses from species B, C, D, E, and F against B-cell cancer cell lines and primary patient cells.
  • In vivo studies using B-cell cancer xenografts in immunodeficient mice to evaluate viral efficacy.
  • Assessment of viral infection, replication, and cell killing capabilities.

Main Results:

  • Species D adenoviruses demonstrated the most effective killing of various B-cell cancer cell lines in vitro.
  • Significant activity was observed against primary marginal zone lymphoma and CD138+ myeloma cells.
  • In vivo, Ad26 and Ad45 (species D) treatments delayed lymphoma xenograft growth.

Conclusions:

  • Species D adenoviruses exhibit unique infectivity and replication in B-cell cancers compared to other adenovirus species.
  • These findings highlight distinct viral biology in B cells, supporting species D adenoviruses as promising oncolytics.
  • Further development of novel species D adenoviruses is warranted for B-cell cancer therapy.

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