Am J Cancer Res. 2021 Oct 15;11(10):5184-5189. eCollection 2021.
ABSTRACT
Transgene-enhanced oncolytic adenoviruses represent a promising novel therapeutic option for the treatment of cancer. A Phase 1 clinical trial featuring AdAPT-001 is ongoing (NCT04673942). AdAPT-001, a type 5 adenovirus, which carries a TGF-β trap transgene that neutralizes the immunosuppressive cytokine, TGF-β, has been shown in an immunocompetent mouse model to eradicate both locally injected and non-injected tumors. Single dose biodistribution of the TGF-β trap transgene was also evaluated in tumor bearing mice, providing an explanation for systemic activity. The biodistribution and toxicity of a single administration of mouse AdAPT-001 (mAdAPT-001) in 129S1 immunocompetent mice bearing ADS-12 tumors (mouse lung carcinoma) were assessed. mAdAPT-001 was injected intratumorally and intravenously in groups of 25 mice each at varying dose levels. Soluble TGF-β trap was detected in the serum using ELISA. A single AdAPT-001 injection resulted in non-negligible long-term TGF-β trap persistence in the serum over the 14-day study after intravenous and intratumoral administration. No TGF-β-related toxicity was observed. At clinically relevant doses, AdAPT-001 was safe and well tolerated. Systemic levels of the TGF-β trap transgene were observed from both local and intravenous dosing.
PMID:34765319 | PMC:PMC8569352
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