Nonclinical characterization of ICVB-1042 as a selective oncolytic adenovirus for solid tumor treatment

Commun Biol. 2024 Sep 13;7(1):1132. doi: 10.1038/s42003-024-06839-6.

Abstract

ICVB-1042 is an oncolytic adenovirus containing modifications to enhance replication, lysis, and viral spreading in tumor cells. The anti-tumor activity, immune activation, tropism, selectivity, and mechanism of action were evaluated in preparation for a first-in-human study. ICVB-1042 was at least 100-fold more cytotoxic in A549 cells than in normal primary cells tested, demonstrating its high tumor selectivity and a low likelihood of targeting primary tissues. ICVB-1042 administered to mice intravenously or intratumorally was effective in reducing tumor burden. Its intravenous administration also inhibited tumor growth in orthotopic models. ICVB-1042 was well tolerated in mice compared to HAdV-C5 (Wt Ad5), with reduced liver sequestration, supporting safety of the drug for systemic delivery. These preclinical data demonstrating the safety and potency of ICVB-1042 for treatment of various solid tumors support the ongoing clinical investigation (NCT05904236).

MeSH terms

  • A549 Cells
  • Adenoviridae* / genetics
  • Animals
  • Cell Line, Tumor
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasms* / therapy
  • Oncolytic Virotherapy* / methods
  • Oncolytic Viruses* / genetics
  • Virus Replication
  • Xenograft Model Antitumor Assays

Associated data

  • ClinicalTrials.gov/NCT05904236