CPC C07K 16/2878 (2013.01) [A61K 31/7076 (2013.01); A61K 35/17 (2013.01); A61K 39/0011 (2013.01); A61K 39/46 (2023.05); A61K 39/4631 (2023.05); A61K 39/464417 (2023.05); C07K 14/7051 (2013.01); C07K 14/70517 (2013.01); C07K 14/70578 (2013.01); C07K 16/2896 (2013.01); C12N 5/0636 (2013.01); C12N 5/10 (2013.01); C12N 15/63 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); A61K 2039/5156 (2013.01); C07K 16/2863 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01); C07K 2317/569 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2317/92 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/33 (2013.01); C12N 2510/02 (2013.01)] | 24 Claims |
1. A method of treating a condition associated with malignant cells expressing B-cell maturation antigen (BCMA) in a subject comprising:
administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising an engineered immune cell expressing at the surface a BCMA-specific chimeric antigen receptor (CAR) comprising an extracellular ligand-binding domain, a first transmembrane domain, and an intracellular signaling domain and wherein the extracellular ligand-binding domain comprises a single chain Fv fragment (scFv) comprising
(i) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 33 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 34;
(ii) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 112 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 38;
(iii) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 72 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 73;
(iv) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 39 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 40;
(v) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 76 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 77;
(vi) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 83 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 84;
(vii) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 92 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 93;
(viii) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 25 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 18; or
(ix) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 8 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 80,
wherein the transmembrane domain comprises a CD8α chain transmembrane domain, and wherein the intracellular signaling domain comprises a CD3ξ signaling domain and/or a 4-1BB signaling domain.
|