Antigen-binding polypeptides directed against CD38
The invention relates to polypeptides specifically binding to CD38 and are therefore suitable for the diagnosis and for the therapeutic and prophylactic treatment of diseases which are characterized by increased CD38 expression. Conjugates and pharmaceutical compositions comprising the polypeptides are disclosed as well. In addition, the invention relates to the use of such polypeptides in methods for the detection of CD38 and/or CD38-expressing cells in a biological sample. A process for the purification and concentration of CD38 and/or CD38-expressing cells in which the antigen-binding polypeptides are used are also described.
1. A method of targeting a CD38-expressing cell for treatment of at least one disease, disorder or condition that is associated with CD38, said method comprising administering a pharmaceutically active amount of a polypeptide to a subject in need thereof, wherein the polypeptide comprises at least one immunoglobulin single variable domain (ISVD) that specifically binds to an epitope on human CD38 (SEQ ID NO:465) with an EC 50 value of less than 200 nM and does not compete with monoclonal anti-CD38 antibody daratumumab binding to said CD38, wherein said at least one ISVD is selected from the group consisting of WF152 (SEQ ID NO:1), JK54 (SEQ ID NO:2), WF9 (SEQ ID NO:3), JK36 (SEQ ID NO: 4), JK30 (SEQ ID NO:5), JK24 (SEQ ID NO:6), JK31 (SEQ ID NO:7), JK32 (SEQ ID NO:8), WF32 (SEQ ID NO:9), JK2 (SEQ ID NO:11), JK12 (SEQ ID NO:12), JK14 (SEQ ID NO:13), and JK42 (SEQ ID NO:14).
2. The method of claim 1 , wherein said CD38-expressing cell is a tumor cell.
3. The method of claim 2 , further comprising administering monoclonal anti-CD38 antibody daratumumab to said subject, wherein said at least one ISVD and said daratumumab bind to non-overlapping epitopes on CD38 of said tumor cell.
4. The method of claim 3 , wherein said at least one ISVD and said daratumumab demonstrate a synergistic cytotoxic effect against said CD38-expressing tumor cell.
5. The method of claim 2 , wherein said polypeptide inhibits growth of said tumor cell.
6. The method of claim 1 , wherein said polypeptide comprises at least a second ISVD that specifically binds to an epitope on human CD38, wherein said at least one ISVD binds a first epitope of CD38 and said second ISVD binds a second epitope on CD38, wherein said first epitope is different from said second epitope.
7. The method of claim 6 , wherein said first epitope does not overlap with said second epitope.
8. The method of claim 6 , wherein said at least two ISVDs are directly linked to each other or linked to each other via a linker.
9. The method of claim 8 , in which the linker is selected from the group of linkers with SEQ ID NOs: 482-494.
10. The method of claim 1 , wherein said ISVD specifically binds a first epitope of said CD38 and wherein daratumumab binds to a second epitope of said CD38, wherein said first epitope and said second epitope are different.
11. The method of claim 10 , wherein said first epitope and said second epitope do not overlap.
12. The method of claim 1 , further comprising a fragment crystallizable portion (Fc portion) linked to said at least one ISVD.
13. The method of claim 1 , said method comprising administering to said subject a composition comprising a plurality of said polypeptides and at least one pharmaceutically acceptable carrier, diluent, excipient, and/or adjuvant.