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Drug intelligence / Profile preview
pH-selective B7-H3 CAR-T cells
- Development stage
- Preclinical
- Lead developer
- Changping Laboratory
- Modality
- CAR-T Cells → Engineered T Cells → Adoptive Cell Transfer → Cell Therapies
- Administration
- Intravenous
01
Overview
pH-selective B7-H3 CAR-T cells are chimeric antigen receptor (CAR) T-cell therapies engineered to selectively target the CD276 antigen (B7-H3) under acidic conditions, such as those found in the solid tumor microenvironment (TME). Developed by Changping Laboratory and West China Hospital of Sichuan University, these CAR-T cells utilize a structure-guided computational approach with in silico dual-pH scanning mutagenesis to introduce histidine or aspartic acid substitutions within the complementarity-determining regions (CDRs) of the single-chain variable fragment (scFv). This design creates a molecular switch that destabilizes CAR binding at physiological pH (7.4) while preserving or enhancing affinity at acidic pH (6.5), thereby mitigating on-target/off-tumor (OTOT) toxicity against healthy tissues that express basal levels of B7-H3.
- Other names
- pH-dependent B7-H3 CAR-T cells
02
Targets
B7-H3
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