BCMA/CD19 CAR FOR TREATING MULTIPLE MYELOMA

1 . A method of treating relapsed or resistant BCMA+ or CD19+ malignancy in a patient comprising administering autologous BCMA/CD19 CAR T-cells to the patient.

2 . (canceled)

3 . The method of claim 1 wherein the BCMA+ or CD19+ malignancy is multiple myeloma (MM) or a BCMA+ or CD19+ plasma cell disorder.

4 . The method of claim 3 wherein the BCMA+ or CD19+ malignancy is multiple myeloma (MM).

5 . The method of claim 1 wherein the patient has:

a) Relapsed or refractory Multiple Myeloma;

b) Secretory disease;

c) ≥3 prior lines of therapy;

d) Refractory to last line of therapy; or

e) Has previously received or is not suitable for autologous stem cell transplant (ASCT).

6 . The method of claim 1 wherein the patient is administered a single dose of 5×10 6 CAR T-cells, 25×10 6 CAR T-cells, 50×10 6 CAR T-cells, or 150×10 6 CAR T-cells.

7 . The method of claim 6 wherein the administration is an intravenous injection through a Hickman line or peripherally inserted central catheter.

8 . The method of claim 1 wherein the BCMA/CD19 CAR T-cell product expresses a chimeric antigen receptor (CAR) comprising a BCMA-binding domain which comprises

a) a heavy chain variable region (VH) having CDRs with the following sequences:

(SEQ ID NO: 1)

CDR1-GFIFSDYN 

(SEQ ID NO: 2)

CDR2-IIYDGSST 

 (SEQ ID NO: 3)

CDR3-ATRPGPFAY;

and

b) a light chain variable region (VL) having CDRs with the following sequences:

 (SEQ ID NO: 4)

CDR1-QSLLHSNGNTY

 (SEQ ID NO: 5)

CDR2-LVS

(SEQ ID NO: 6)

CDR3-VHGTHAWT.

9 . The method of claim 8 , wherein the BCMA-binding domain comprises a VH domain having the sequence shown as SEQ ID NO: 7 and/or or a VL domain having the sequence shown as SEQ ID NO: 8 or a variant thereof having at least 95% sequence identity.

10 . The method of claim 8 , wherein the BCMA-binding domain comprises an scFv in the orientation VH-VL.

11 . The method of claim 8 , wherein the BCMA-binding domain comprises a Fab.

12 . The method of claim 11 , wherein the BCMA-binding Fab comprises a heavy chain (VH-CH1) sequence shown as SEQ ID NO: 9.

13 . The method of claim 11 , wherein the BCMA-binding Fab comprises a light chain (VL-CL kappa) sequence shown as SEQ ID NO: 10.

14 - 18 . (canceled)

19 . The method of claim 1 wherein the BCMA/CD19 CAR T-cell product expresses a chimeric antigen receptor (CAR) comprising a CD19-binding domain which comprises

a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences:

 (SEQ ID NO: 37)

CDR1-GYAFSSS;

 (SEQ ID NO: 38)

CDR2-YPGDED

 (SEQ ID NO: 39)

CDR3-SLLYGDYLDY;

and

b) a light chain variable region (VL) having CDRs with the following sequences:

 (SEQ ID NO: 40)

CDR1-SASSSVSYMH;

 (SEQ ID NO: 41)

CDR2-DTSKLAS

(SEQ ID NO: 42)

CDR3-QQWNINPLT.

20 . The method of claim 19 , wherein the CD19-binding domain comprises a VH domain having the sequence shown as SEQ ID NO: 43 and/or or a VL domain having the sequence shown as SEQ ID NO: 44 or a variant thereof having at least 95% sequence identity.

21 . The method of claim 19 , wherein the CD19-binding domain comprises an scFv in the orientation VH-VL.

22 . The method of claim 21 , wherein the CD19-binding domain comprises the sequence shown as SEQ ID NO: 45 or a variant thereof having at least 90% sequence identity.

23 - 27 . (canceled)

28 . The method of claim 1 wherein the autologous CD19/22 CAR T-cells comprise the BCMA/CD19 CAR T-cell product comprising D8 FabCAR and CAT19CAR CARs.