Chimeric antigen receptor (CAR) comprising a CD22-binding domain
The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising an antigen-binding domain, wherein the antigen-binding domain of the first CAR binds to CD19 and the antigen-binding domain of the second CAR binds to CD22.
1. A chimeric antigen receptor (CAR) comprising a CD22-binding domain which comprises:
a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences:
CDR1
(SEQ ID NO: 27)
NYWIN,
CDR2
(SEQ ID NO: 28)
NIYPSDSFTNYNQKFKD,
and
CDR3
(SEQ ID NO: 29)
DTQERSWYFDV;
and
b) a light chain variable region (VL) having CDRs with the following sequences:
CDR1
(SEQ ID NO: 30)
RSSQSLVHSNGNTYLH,
CDR2
(SEQ ID NO: 31)
KVSNRFS,
and
CDR3
(SEQ ID NO: 32)
SQSTHVPWT.
2. A CAR according to claim 1 , wherein the CD22 binding domain comprises a VH domain having the sequence shown as SEQ ID NO: 35 or SEQ ID NO: 36, or a VL domain having the sequence shown as SEQ ID NO: 37 or SEQ ID NO: 38.
3. A CAR according to claim 1 , wherein the CD22 binding domain comprises the sequence shown as SEQ ID NO: 33 or SEQ ID NO: 34.
4. A cell comprising a CAR according to claim 1 .
5. A nucleic acid sequence encoding a CAR according to claim 1 .
6. A vector which comprises a nucleic acid sequence according to claim 5 .
7. A method for making a cell comprising CAR comprising a CD22-binding domain which comprises:
a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences:
CDR1
(SEQ ID NO: 27)
NYWIN,
CDR2
(SEQ ID NO: 28)
NIYPSDSFTNYNQKFKD,
CDR3
(SEQ ID NO: 29)
DTQERSWYFDV;
and
b) a light chain variable region (VL) having CDRs with the following sequences:
CDR1
(SEQ ID NO: 30)
RSSQSLVHSNGNTYLH,
CDR2
(SEQ ID NO: 31)
KVSNRFS,
CDR3
(SEQ ID NO: 32)
SQSTHVPWT,
wherein the method comprises the step of introducing into a cell a nucleic acid sequence encoding the CAR or a vector comprising a nucleic acid encoding the CAR.
8. A pharmaceutical composition comprising a plurality of cells according to claim 4 .