CD33-Binding Polypeptides and Uses Thereof
Provided herein are VHH-containing polypeptides that bind CD33. Uses of the VHH-containing polypeptides are also provided.
1 . A polypeptide comprising at least one VHH domain that binds CD33, wherein at least one VHH domain that binds CD33 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 56; a CDR2 comprising the amino acid sequence of SEQ ID NO: 54 or 57; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
2 - 4 . (canceled)
5 . The polypeptide of claim 1 , wherein at least one VHH domain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 56; a CDR2 comprising the amino acid sequence of SEQ ID NO: 54; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
6 . The polypeptide of claim 1 , wherein at least one VHH domain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 56; a CDR2 comprising the amino acid sequence of SEQ ID NO: 57; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
7 - 11 . (canceled)
12 . The polypeptide of claim 1 , wherein at least one VHH domain is humanized.
13 . The polypeptide of claim 1 , wherein at least one VHH domain comprises an amino acid sequence at least 85%, at least 90%, at least 95%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 40, 41, 116, or 117.
14 . The polypeptide of claim 1 , wherein at least one VHH domain comprises the amino acid sequence of SEQ ID NO: 40, 41, 116, or 117.
15 . (canceled)
16 . (canceled)
17 . The polypeptide of claim 1 , comprising one, two, or three VHH domains.
18 . (canceled)
19 . The polypeptide of claim 1 , wherein the polypeptide comprises at least one binding domain that binds an antigen other than CD33.
20 . The polypeptide of claim 19 , wherein the polypeptide comprises at least one binding domain that binds CD3, T-cell receptor (TCR)α, TCRβ, CD28, CD16, CD32A, CD64, CD89, NKp46, or NKG2D.
21 . The polypeptide of claim 17 , wherein each VHH domain binds CD33.
22 .- 24 . (canceled)
25 . The polypeptide of claim 1 , wherein the polypeptide comprises an Fc region.
26 . The polypeptide of claim 25 , wherein the Fc region comprises an amino acid sequence selected from SEQ ID NOs: 74-109.
27 . The polypeptide of claim 25 , which forms a dimer under physiological conditions.
28 . (canceled)
29 . (canceled)
30 . An immunoconjugate comprising the polypeptide of claim 1 and a cytotoxic agent.
31 . The immunoconjugate of claim 30 , wherein the cytotoxic agent is selected from a calicheamicin, an auristatin, a dolastatin, a tubulicin, a maytansinoid, a cryptophycin, a duocarmycin, an esperamicin, a pyrrolobenzodiazepine, and an enediyne antibiotic.
32 . A pharmaceutical composition comprising the polypeptide of claim 1 , and a pharmaceutically acceptable carrier.
33 - 38 . (canceled)
39 . A method of treating cancer comprising administering to a subject with cancer a pharmaceutically effective amount of the polypeptide of claim 1 .
40 . The method of claim 39 , wherein the cancer is selected from lymphoma; Hodgkin's lymphoma; non-Hodgkin's lymphoma; B-cell lymphoma; low grade/follicular non-Hodgkin's lymphoma (NHL); small lymphocytic (SL) NHL; intermediate grade/follicular NHL; intermediate grade diffuse NHL; high grade immunoblastic NHL; high grade lymphoblastic NHL; high grade small non-cleaved cell NHL; bulky disease NHL; mantle cell lymphoma; AIDS-related lymphoma; Waldenstrom's macroglobulinemia; chronic lymphocytic leukemia (CLL); acute lymphoblastic leukemia (ALL); acute myeloid leukemia (AML); Hairy cell leukemia; and chronic myeloblastic leukemia.
41 . (canceled)
42 . The method of claim 39 , further comprising administering an additional therapeutic agent.
43 . The method of claim 42 , wherein the additional therapeutic agent is an anti-cancer agent, wherein the anti-cancer agent is selected from a chemotherapeutic agent, an anti-cancer biologic, radiation therapy, CAR-T therapy, and an oncolytic virus.
44 . (canceled)
45 . (canceled)