Ultralow-dose binary oncolytic/helper-dependent adenovirus promotes antitumor activity in preclinical and clinical studies

Daniel Wang, Caroline E. Porter, Bora Lim, Amanda Rosewell Shaw, Catherine S. Robertson, Mae L. Woods, Ya Xu, Greyson G.W. Biegert, Daisuke Morita, Tao Wang, Bambi J. Grilley, Helen Heslop, Malcolm K. Brenner, Masataka Suzuki

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

We show that a binary oncolytic/helper-dependent adenovirus (CAdVEC) that both lyses tumor cells and locally expresses the proinflammatory cytokine IL-12 and PD-L1 blocking antibody has potent antitumor activity in humanized mouse models. On the basis of these preclinical studies, we treated four patients with a single intratumoral injection of an ultralow dose of CAdVEC (NCT03740256), representing a dose of oncolytic adenovirus more than 100-fold lower than used in previous trials. While CAdVEC caused no significant toxicities, it repolarized the tumor microenvironment with increased infiltration of CD8 T cells. A single administration of CAdVEC was associated with both locoregional and abscopal effects on metastases and, in combination with systemic administration of immune checkpoint antibodies, induced sustained antitumor responses, including one complete and two partial responses. Hence, in both preclinical and clinical studies, CAdVEC is safe and even at extremely low doses is sufficiently potent to induce significant tumor control through oncolysis and immune repolarization.

Original languageEnglish (US)
Article numbereade6790
Pages (from-to)eade6790
JournalScience advances
Volume9
Issue number13
DOIs
StatePublished - Mar 29 2023

Keywords

  • Mice
  • Animals
  • Oncolytic Virotherapy/adverse effects
  • Oncolytic Viruses
  • Adenoviridae/genetics
  • Neoplasms/pathology
  • Cytokines
  • Cell Line, Tumor
  • Tumor Microenvironment

ASJC Scopus subject areas

  • General

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