Chimeric antigen receptor
The present invention provides a chimeric antigen receptor (CAR) which binds a target antigen having a bulky extracellular domain, wherein the CAR comprises a Fab antigen binding domain. The present invention also provides nucleic acid sequences and constructs encoding such a CAR, cells expressing such a CAR and their therapeutic uses.
1. A cytolytic T cell expressing an anti-CD22 chimeric antigen receptor (CAR) and an anti-CD19 CAR, wherein:
a) the anti-CD22 CAR comprises a VH domain comprising the sequence of SEQ ID NO: 65 and a VL domain comprising the sequence of SEQ ID NO: 66, human CD8 stalk and transmembrane domain, human 4-1BB co-stimulatory domain and human CD3ζ endodomain, and
b) the anti-CD19 CAR comprises a VH domain comprising the sequence of SEQ ID NO: 75 and a VL domain comprising the sequence of SEQ ID NO: 76, human CD8 stalk and transmembrane domain, human 4-1BB co-stimulatory domain and human CD3ζ endodomain.
2. A pharmaceutical composition comprising a plurality of cells according to claim 1 , together with a pharmaceutically acceptable carrier, diluent or excipient.
3. A method for treating a B-cell leukemia or lymphoma expressing CD22 and/or CD19 in a human subject comprising administering the pharmaceutical composition of claim 2 to the subject.
4. The method of claim 3 , wherein the B-cell leukemia is an Acute Lymphoblastic Leukaemia (ALL).
5. A method for making a cell according to claim 1 comprising introducing into the cell ex vivo:
a) a vector encoding the anti-CD22 CAR of part a) of claim 1 , and
b) a vector encoding the anti-CD19 CAR of part b) of claim 1 .
6. A kit comprising:
a) a vector encoding an anti-CD22 CAR, wherein the anti-CD22 CAR comprises a VH domain comprising the sequence of SEQ ID NO: 65 and a VL domain comprising the sequence of SEQ ID NO: 66, human CD8 stalk and transmembrane domain, human 4-1BB co-stimulatory domain and human CD3ζ endodomain, and
b) a vector encoding an anti-CD19 CAR, wherein the anti-CD19 CAR comprises a VH domain comprising the sequence of SEQ ID NO: 75 and a VL domain comprising the sequence of SEQ ID NO: 76, human CD8 stalk and transmembrane domain, human 4-1BB co-stimulatory domain and human CD3ζ endodomain.