Chimeric antigen receptors targeting b-cell maturation antigen and methods of use thereof
OwnerDavid Chang, Arun Balakumaran +1inventors
InventorsDavid Chang, Arun Balakumaran, Cyril Alkis Konto
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Abstract
Provided herein are BCMA CARs and CAR-T cells, methods of making, and using the same. In some embodiments, particular dosing regimens, redosing regimens, and combination regimens with lymphodepletion are provided, for the treatment and clinical management of multiple myeloma in subjects in need thereof.
Claims51
A method of treating multiple myeloma in a subject comprising administering to the subject at least one dose of allogeneic chimeric antigen receptor (CAR)-T cells comprising an anti-human BCMA CAR (BCMA CAR-T cells), wherein the at least one dose is about 7×10{circumflex over ( )}6 cells/dose to about 480×10{circumflex over ( )}6 cells/dose.
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A formulation comprising BCMA CAR-T cells, wherein the cells are formulated in a solution comprising about 5% dimethyl sulfoxide, wherein the dosage strength of the formulation is 14×10{circumflex over ( )}6 cells/mL, wherein the genotype of the cells is BCMA-CAR+_TCRαβ_CD52+/−, and wherein the BCMA CAR-T cells comprise a CAR comprising an extracellular ligand-binding domain, two rituximab-binding domains, a first transmembrane domain, and an intracellular signaling domain, wherein the extracellular domain comprises a scFv comprising a heavy chain variable (VH) region comprising a sequence shown in SEQ ID NO:
- 33, 72, 39, 76, 83, 92, 25, 112, or 8 of Table 1;
- and a light chain variable (VL) region comprising a sequence shown in SEQ ID NO:
- 34, 73, 40, 77, 84, 93, 18, 38, or 80 of Table 1, wherein the first transmembrane domain comprises a CD8α chain transmembrane domain, and wherein the intracellular signaling domain comprises a CD3ζ signaling domain and/or a 4-1BB signaling domain.
A formulation comprising BCMA CAR-T cells, wherein the cells are formulated in a 1:1 mixture of CryoStor® Basal Solution and CryoStor® CS10 resulting in a 5% final concentration of dimethyl sulfoxide, wherein the dosage strength of the formulation is 14×10{circumflex over ( )}6 cells/mL, wherein the genotype of the cells is BCMA-CAR+_TCRαβ-_CD52+/−, and wherein the BCMA CAR-T cells comprise a CAR comprising an extracellular ligand-binding domain, two rituximab-binding domains, a first transmembrane domain, and an intracellular signaling domain, wherein the extracellular domain comprises a scFv comprising a heavy chain variable (VH) region comprising a sequence shown in SEQ ID NO:
- 33, 72, 39, 76, 83, 92, 25, 112, or 8 of Table 1;
- and a light chain variable (VL) region comprising a sequence shown in SEQ ID NO:
- 34, 73, 40, 77, 84, 93, 18, 38, or 80 of Table 1, wherein the first transmembrane domain comprises a CD8α chain transmembrane domain, and wherein the intracellular signaling domain comprises a CD3ζ signaling domain and/or a 4-1BB signaling domain.
Dependencies are inferred from the claim text.