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wild-type ADA2
- Development stage
- Discontinued
- Lead developer
- Halozyme
- Modality
- Recombinant Proteins and Enzymes
- Administration
- Intravenous
01
Overview
Wild-type ADA2 (wtADA2) is a recombinant form of the human enzyme adenosine deaminase 2, which was investigated by Halozyme Therapeutics as a potential immunotherapeutic agent for the treatment of solid tumors. The enzyme functions by catalyzing the deamination of adenosine, an endogenous immunosuppressant that often accumulates at high levels within the tumor microenvironment (TME) to protect tumors from immune-mediated rejection. By depleting TME adenosine, ADA2 aims to stimulate anti-tumor immune activity. However, preclinical evaluations revealed that wtADA2 has an extremely rapid systemic clearance, with a circulating half-life of approximately 69 minutes in mice, rendering the wild-type protein unsuitable for clinical development. This limitation led to the engineering of pegylated and modified variants, such as PEG-ADA2-K374D and PEG-ADA2-R222Q-S265N, which exhibit significantly improved pharmacokinetics and anti-tumor efficacy.
- Other names
- adenosine deaminase 2recombinant wild-type ADA2
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