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AssigneeAutolus Limited
InventorsMartin Pulé, Anne Kramer, Leila Mekkaoui, Persis Amrolia, Sara Ghorashian, Gordon Cheung
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There is provided 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. 1) CDR1 - GYAFSSS; (SEQ ID No. 2) CDR2 - YPGDED (SEQ ID No. 3) CDR3 - SLLYGDYLDY; and b) a light chain variable region (VL) having CDRs with the following sequences: (SEQ ID No. 4) CDR1 - SASSSVSYMH; (SEQ ID No. 5) CDR2 - DTSKLAS (SEQ ID No. 6) CDR3 - QQWNINPLT. There is also provided a cell comprising such a CAR, and the use of such a cell in the treatment of cancer, in particular a B cell malignancy.
A chimeric antigen receptor (CAR) comprising a CD19-binding domain which comprises
A CAR according to any preceding claim, wherein CD19-binding domain and the transmembrane domain are connected by a spacer.
A CAR according to any preceding claim which also comprises an intracellular T cell signalling domain.
A CAR according to any preceding claim, which comprises the sequence shown as any of SEQ ID No. 10 to 15 or a variant thereof which has at least 80% sequence identity but retains the capacity to i) bind CD19 and ii) induce T cell signalling.
A CAR according to any preceding claim which, when expressed by a T-cell and used to target a CD19 expressing cell, causes lower IFNγ release by the CD19-expressing target cell than that caused by a T-cell expressing a CAR comprising a CD19-binding domain which comprises
A CAR according to any preceding claim wherein the CDRs are grafted on to a human or humanised framework.
A nucleic acid sequence which encodes a CAR according to any preceding claim.
Dependencies are inferred from the claim text.