Chimeric antigen receptors targeting FLT3
AssigneePfizer Inc.
InventorsBarbra Johnson Sasu, Danielle Elizabeth Dettling, Cesar Adolfo Sommer, Yik Andy Yeung, Moustafa Marc Hamze
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Abstract
Provided herein are antibodies that specifically bind to Fms-like tyrosine kinase 3 (FLT3), chimeric antigen receptors (CARs) that specifically bind to FLT3, and engineered immune cells expressing such CARs (e.g. FLT3-specific CAR-T cells). The invention also provides making such antibodies, CARs, and engineered immune cells. The invention also provides using such antibodies, CARs, and engineered immune cells, for example for the treatment of a condition associated with malignant cells expressing FLT3 (e.g., cancer).
Claims24
A Fms-like tyrosine kinase 3 (FLT3) specific chimeric antigen receptor (CAR) comprising an extracellular ligand-binding domain, a first transmembrane domain, and an intracellular signaling domain, wherein the extracellular ligand-binding domain comprises a single chain variable fragment (scFv) comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein:
- (a) the VH region comprises (i) a VH complementarity determining region one (CDR1) having the amino acid sequence shown in SEQ ID NO:
- 90, 91, or 92, (ii) a VH complementarity determining region two (CDR2) having the amino acid sequence shown in SEQ ID NO:
- 93 or 94, and (iii) a VH complementarity determining region three (CDR3) having the amino acid sequence shown in SEQ ID NO:
- 95;
- and
- the VL region comprises (i) a VL complementarity determining region one (CDR1) having the amino acid sequence shown in SEQ ID NO:
- 171;
- (ii) a VL complementarity determining region two (CDR2) having the amino acid sequence shown in SEQ ID NO:
- 172;
- and (iii) a VL complementarity determining region three (CDR3) having the amino acid sequence shown in SEQ ID NO:
- 173;
- (b) the VH region comprises a VH CDR1 comprising the amino acid sequence shown in SEQ ID NO:
- 49, 44, or 50;
- a VH CDR2 comprising the amino acid sequence shown in SEQ ID NO:
- 51 or 52;
- and a VH CDR3 comprising the amino acid sequence shown in SEQ ID NO:
- 53;
- and the VL region comprises a VL CDR1 comprising the amino acid sequence shown in SEQ ID NO:
- 150;
- a VL CDR2 comprising the amino acid sequence shown in SEQ ID NO:
- 151;
- and a VL CDR3 comprising the amino acid sequence shown in SEQ ID NO:
- 152;
- (c) the VH region comprises a VH CDR1 comprising the amino acid sequence shown in SEQ ID NO:
- 60, 61, or 62;
- a VH CDR2 comprising the amino acid sequence shown in SEQ ID NO:
- 63 or 64;
- and a VH CDR3 comprising the amino acid sequence shown in SEQ ID NO:
- 65;
- and the VL region comprises a VL CDRI comprising the amino acid sequence shown in SEQ ID NO:
- 156;
- a VL CDR2 comprising the amino acid sequence shown in SEQ ID NO:
- 157;
- and a VL CDR3 comprising the amino acid sequence shown in SEQ ID NO:
- 158;
- (d) the VH region comprises a VH CDR1 comprising the amino acid sequence shown in SEQ ID NO:
- 84, 85, or 86;
- a VH CDR2 comprising the amino acid sequence shown in SEQ ID NO:
- 87 or 88;
- and a VH CDR3 comprising the amino acid sequence shown in SEQ ID NO:
- 89;
- and the VL region comprises a VL CDR1 comprising the amino acid sequence shown in SEQ ID NO:
- 168;
- a VL CDR2 comprising the amino acid sequence shown in SEQ ID NO:
- 169;
- and a VL CDR3 comprising the amino acid sequence shown in SEQ ID NO:
- 170;
- or
- (e) the VH region comprises a VH CDR1 comprising the amino acid sequence shown in SEQ ID NO:
- 108, 109, or 110;
- a VH CDR2 comprising the amino acid sequence shown in SEQ ID NO:
- 111 or 112;
- and a VH CDR3 comprising the amino acid sequence shown in SEQ ID NO:
- 113;
- and the VL region comprises a VL CDR1 comprising the amino acid sequence shown in SEQ ID NO:
- 180;
- a VL CDR2 comprising the amino acid sequence shown in SEQ ID NO:
- 181;
- and a VL CDR3 comprising the amino acid sequence shown in SEQ ID NO:
- 182.
Dependencies are inferred from the claim text.