Nonclinical characterization of ICVB-1042 as a selective oncolytic adenovirus for solid tumor treatment
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).
Authors
- Jinkil Jeong (ORCID: https://orcid.org/0000-0001-6616-9245)
- Nathaniel Rice (ORCID: https://orcid.org/0000-0003-2859-4616)
- Michael Pokrass (ORCID: https://orcid.org/0000-0002-9603-4189)
- Yu Kato (ORCID: https://orcid.org/0000-0003-4743-1775)
- Rubén Rodríguez (ORCID: https://orcid.org/0000-0001-8174-2556)
- Heba Nowyhed
- Jessica J. Field (ORCID: https://orcid.org/0000-0003-4390-0829)
Institutions
- Hebrew Union College - Jewish Institute of Religion (US)
Publication Details
- Journal
- Communications Biology
- Published
- 2024-09-13
- DOI
- https://doi.org/10.1038/s42003-024-06839-6
- Citations
- 4
- Primary Topic
- Virus-based gene therapy research
- Type
- article
- Field-Weighted Citation Impact
- 2.20