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Nonclinical characterization of ICVB-1042 as a selective oncolytic adenovirus for solid tumor treatment
Yu Kato1, Nathaniel Rice1, Michael Pokrass1
1IconOVir Bio, New York, NY, USA.
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).
Insights
ICVB-1042, an oncolytic adenovirus, shows potent anti-tumor activity and high tumor selectivity. Preclinical studies in mice demonstrate its safety and efficacy for treating solid tumors, supporting clinical trials.
Area of Science:
- Oncolytic virotherapy
- Adenovirus vector engineering
- Cancer immunotherapy
Background:
- Oncolytic viruses selectively infect and kill cancer cells, stimulating an anti-tumor immune response.
- Adenovirus vectors are being engineered for enhanced oncolytic properties and improved safety profiles.
- ICVB-1042 is a modified oncolytic adenovirus designed for enhanced tumor cell replication, lysis, and spread.
Purpose of the Study:
- To evaluate the anti-tumor activity, immune activation, tropism, selectivity, and mechanism of action of ICVB-1042.
- To assess the safety and tolerability of ICVB-1042 in preclinical models.
- To provide data supporting the initiation of a first-in-human clinical study.
Main Methods:
- In vitro cytotoxicity assays using tumor and normal primary cells (e.g., A549 cells).
- In vivo efficacy studies in mice with intravenous and intratumoral administration of ICVB-1042.
- Pharmacokinetic and biodistribution studies, including liver sequestration assessment compared to wild-type Adenovirus type 5 (Wt Ad5).
Main Results:
- ICVB-1042 demonstrated over 100-fold greater cytotoxicity in A549 tumor cells compared to normal primary cells, indicating high tumor selectivity.
- Both intravenous and intratumoral administration of ICVB-1042 effectively reduced tumor burden in mice.
- Intravenous ICVB-1042 administration inhibited tumor growth in orthotopic models and was well tolerated, with reduced liver sequestration compared to Wt Ad5.
Conclusions:
- ICVB-1042 exhibits potent anti-tumor efficacy and favorable safety profile in preclinical models.
- The demonstrated tumor selectivity and efficacy support ICVB-1042's potential as a treatment for various solid tumors.
- These findings provide a strong rationale for the ongoing clinical investigation of ICVB-1042.
