Bi-specific chimeric antigen receptor
AssigneeThe Regents of the University of California
InventorsYvonne Yu-Hsuan Chen, Zenan Li Chang
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Abstract
Aspects of the disclosure relate to polypeptides comprising a signal peptide, an antigen-binding domain that specifically binds TGF-β, a peptide spacer, a transmembrane domain, and an endodomain. When expressed in a cell, the polypeptides are capable of not only neutralizing the TGF-β but also specifically triggering T-cell activation in the presence of TGF-β. T-cell activation spurs the immune cell to produce immunostimulatory cytokines and proliferate, thus turning TGF-β from an immunosuppressive signal to an activating stimulus.
Claims10
A polypeptide comprising a bi-specific chimeric antigen receptor (CAR), wherein the CAR comprises a signal peptide, an anti-TGF-β region comprising a variable heavy (VH) and variable light (VL) region, an IL13Rα2 binding region, a peptide spacer, a transmembrane domain, and an endodomain;
- wherein the anti-TGF-β region comprises:
- i) a VH region comprising SEQ ID NO:5 (HCDR1), SEQ ID NO:6 (HCDR2);
- and SEQ ID NO:
- 7 (HCDR3) and a VL region comprising SEQ ID NO:8 (LCDR1), SEQ ID NO:9 (LCDR2);
- and SEQ ID NO:10 (LCDR3);
- ii) a VH region comprising SEQ ID NO:11 (HCDR1), SEQ ID NO:12 (HCDR2);
- and SEQ ID NO:
- 13 (HCDR3) and a VL region comprising SEQ ID NO:14 (LCDR1), SEQ ID NO:15 (LCDR2);
- and SEQ ID NO:16 (LCDR3);
- or
- iii) a VH region comprising SEQ ID NO:21 (HCDR1), SEQ ID NO:22 (HCDR2);
- and SEQ ID NO:23 (HCDR3) and a VL region comprising SEQ ID NO:24 (LCDR1), SEQ ID NO:25 (LCDR2);
- and SEQ ID NO:26 (LCDR3).
Dependencies are inferred from the claim text.