CD22 TARGETING PORTION FOR THE TREATMENT OF B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (B-ALL)

Abstract

The present invention relates to a CD22 targeting portion, characterized in that the CD22 targeting portion has binding affinity for the region of the first extracellular Ig domain of the CD22 antigen defined as SEQ ID NO: 15, and wherein the CD22 targeting portion comprises a VL domain and a VH domain, wherein the VL domain comprises LCDR1, LCDR2, and LCDR3 polypeptides and the VH domain comprises HCDR1, HCDR2, and HCDR3 polypeptides, and wherein LCDR1 consists of [QSLLDSDGKTY] (SEQ ID NO: 1), LCDR2 consists of [LVS] (SEQ ID NO: 2), LCDR3 consists of [WQGTHFPWT] (SEQ ID NO: 3), HCDR1 consists of [GDSITSGY] (SEQ ID NO: 4), HCDR2 consists of [ISYSGST] (SEQ ID NO: 5), and HCDR3 consists of in [ARYPSPDAMNY] (SEQ ID NO: 6).

Claims

1. A CD22 targeting portion, characterized in that the CD22 targeting portion has binding affinity for the region of the first extracellular Ig domain of the CD22 antigen defined as SEQ ID NO 15, and wherein the CD22 targeting portion is an antibody, F(ab')2, Fab, scFab or scFv, comprising a VL domain and a VH domain, wherein the VL domain consists of SEQ ID NO: 7 and the VH domain consists of SEQ ID NO:

8.

2. The CD22 addressing portion according to claim 1, further characterized in that the CD22 addressing portion is an scFv comprising a VL domain and a VH domain, wherein the VL domain consists of SEQ ID NO: 7 and the VH domain consists of SEQ ID NO:

8.

3. The CD22 addressing portion according to claim 2, further characterized in that the CD22 addressing portion is an scFv consisting of SEQ ID NO:

9.

4. A chimeric antigen receptor (CAR) characterized in that it comprises: a. an extracellular domain comprising a CD22 targeting portion, wherein the CD22 targeting portion is as defined in claim 1; b. a transmembrane domain; and c. an intracellular signaling domain.

5. The CAR according to claim 4, further characterized in that the transmembrane domain comprises the transmembrane domain of CD28, CD3, CD45, CD4, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137 or CD154.

6. The CAR according to claim 5, further characterized in that the transmembrane domain comprises the CD8 transmembrane domain.

7. The CAR according to any of claims 4 to 6, further characterized in that the intracellular signaling domain comprises the intracellular domain of CD3ζ, FcRy, CD3y, CD3Ó, CD3s, CD5, CD22, CD79a, CD79b or CD66b.

8. The CAR according to claim 7, further characterized in that the intracellular signaling domain comprises the intracellular domain of CD3ζ.

9. The CAR according to any of claims 4 to 8, further characterized in that the CAR additionally comprises a co-stimulatory signaling domain, preferably the co-stimulatory signaling domain comprises the intracellular domain of CD27, CD28, CD137, CD134, CD30, CD40, lymphocyte function-associated antigen 1 (LFA-1), CD2, CD7, LIGHT, NKG2C or CD276.

10. The CAR according to claim 9, further characterized in that the co-stimulatory signaling domain comprises the intracellular domain of CD137.

11. The CAR according to any of claims 4 to 10, further characterized in that the addressing portion to CD22 is an scFV, preferably the scFV comprises a VL domain consisting of SEQ ID NO: 7 and a VH domain consisting of SEQ ID NO:

8.

12. A nucleic acid characterized in that it encodes for the CAR according to any of claims 4 to 11. iviA / a / zuzz / uii zou 13. A T cell characterized in that it comprises the nucleic acid according to claim 12.

14. The cell according to claim 13 or the CD22 targeting portion according to any of claims 1 to 3, for use in a method for treating a CD22-positive cancer, wherein the method comprises administering the cell or composition to a patient in need thereof, and wherein the CD22-positive cancer is B-cell acute lymphoblastic leukemia (B-ALL), more particularly a relapse of CD19-positive B-ALL.