CD22 antibodies and methods of using the same
The present disclosure relates generally to immunoglobulin-related compositions (e.g., antibodies or antigen binding fragments thereof) that can bind to the CD22 protein. The antibodies of the present technology are useful in methods for detecting and treating a CD22-associated cancer, a CD22-associated autoimmune disease, or a CD22-associated allergy in a subject in need thereof.
1 . An antibody or antigen binding fragment thereof comprising a heavy chain immunoglobulin variable domain (V H ) and a light chain immunoglobulin variable domain (V L ), wherein:
(a) the V H comprises an amino acid sequence selected from the group consisting of: SEQ ID NOs: 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 16; and
(b) the V L comprises an amino acid sequence selected from the group consisting of: SEQ ID NO: 21, and SEQ ID NO: 22, wherein
the antibody or antigen binding fragment binds to a CD22 polypeptide comprising an Ig-like C2-type 1 domain and/or an Ig-like C2-type 2 domain, or
the antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, or a bispecific antibody, or the antigen binding fragment is selected from the group consisting of Fab, F(ab′) 2 , Fab′, scF v , and F v , or
wherein the bispecific antibody binds to T cells, B-cells, myeloid cells, plasma cells, or mast-cells, or wherein the bispecific antibody or antigen binding fragment binds to CD3, CD4, CD8, CD20, CD19, CD21, CD23, CD46, CD80, HLA-DR, CD74, CD22, CD14, CD15, CD16, CD123, TCR gamma/delta, NKp46, KIR, or a small molecule DOTA hapten, or
wherein the bispecific antibody or antigen binding fragment comprises an amino acid sequence selected from any one of SEQ ID NOs: 59-82.
2 . The antibody or antigen binding fragment of claim 1 , further comprising a Fc domain of an isotype selected from the group consisting of IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgD, and IgE, optionally wherein
IgG1 comprises one or more amino acid substitutions selected from the group consisting of N297A and K322A; or
IgG4 comprises a S228P mutation, or
the antibody lacks α-1,6-fucose modifications.
3 . The antibody, or antigen binding fragment, of claim 1 , comprising a heavy chain (HC) amino acid sequence comprising SEQ ID NO: 29, SEQ ID NO: 33, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 44, or SEQ ID NO: 46, and a light chain (LC) amino acid sequence comprising SEQ ID NO: 27, SEQ ID NO: 31, SEQ ID NO: 39, SEQ ID NO: 41, SEQ ID NO: 43, or SEQ ID NO: 45.
4 . The antibody, or antigen binding fragment, of claim 1 , comprising a HC amino acid sequence and a LC amino acid sequence selected from the group consisting of:
SEQ ID NO: 29 and SEQ ID NO: 27 (BC270-hLL2 x CD3 BsAb);
SEQ ID NO: 33 and SEQ ID NO: 31 (BC251-hLL2 x CD3 BsAb);
SEQ ID NO: 40 and SEQ ID NO: 39 (VL1VH4 x mC825);
SEQ ID NO: 42 and SEQ ID NO: 41 (VL1VH4 x hC825);
SEQ ID NO: 44 and SEQ ID NO: 43 (VL1VH10 x mC825); and
SEQ ID NO: 46 and SEQ ID NO: 45 (VL1VH10 x hC825), respectively.
5 . The bispecific antibody or antigen binding fragment of claim 4 or a bispecific antibody or antigen binding fragment comprising an amino acid sequence selected from any one of SEQ ID NOs: 59-82, wherein the bispecific antibody binds to a radiolabeled DOTA hapten and a CD22 antigen.
6 . A recombinant nucleic acid sequence encoding the antibody or antigen binding fragment of claim 3 .
7 . A host cell or vector comprising the recombinant nucleic acid sequence of claim 6 .
8 . A composition comprising the antibody or antigen binding fragment of claim 1 and a pharmaceutically-acceptable carrier, wherein the antibody or antigen binding fragment is optionally conjugated to an agent selected from the group consisting of isotopes, dyes, chromagens, contrast agents, drugs, toxins, cytokines, enzymes, enzyme inhibitors, hormones, hormone antagonists, growth factors, radionuclides, metals, liposomes, nanoparticles, RNA, DNA or any combination thereof.
9 . A kit comprising the antibody or antigen binding fragment of claim 1 and instructions for use, optionally wherein the antibody or antigen binding fragment is coupled to at least one detectable label selected from the group consisting of a radioactive label, a fluorescent label, a chromogenic label and a detectably labeled secondary antibody that specifically binds to the antibody or antigen binding fragment.
10 . A method for treating a CD22-associated cancer, a CD22-associated autoimmune disease, or a CD22-associated allergy in a subject in need thereof, comprising administering to the subject an effective amount of the antibody, or antigen binding fragment, of claim 4 or a bispecific antibody, or antigen binding fragment thereof, comprising an amino acid sequence selected from any one of SEQ ID NOs: 59-82.
11 . The method of claim 10 wherein,
the CD22-associated cancer is acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia, chronic lymphocytic leukemia, Non-Hodgkin Lymphoma, multiple myeloma, Plasmacytoma, Monoclonal gammopathy of undetermined significance, Waldenstrom's macroglobulinemia (lymphoplasmacytic lymphoma), Heavy chain disease, primary amyloidosis, Post-transplant lymphoproliferative disorder, Hodgkin lymphoma, MALT lymphoma, B cell Lymphoma, mantle cell lymphoma, diffuse large cell lymphoma, Burkitt's lymphoma, Bilineage leukemia, biphenotypic leukemia, Hairy cell leukemia, Precursor B acute lymphoblastic leukemia/lymphoma, Primary cutaneous follicle center lymphoma, follicular lymphoma, or Marginal Zone B-cell Non-Hodgkin's Lymphoma, or
the CD22-associated autoimmune disease is multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus, paraneoplastic syndromes, Pemphigus Vulgaris, type 2 diabetes, or graft-versus-host disease.
12 . The method of claim 10 , wherein the antibody or antigen binding fragment is administered to the subject separately, sequentially or simultaneously with an additional therapeutic agent.
13 . A method for detecting a tumor in a subject in vivo comprising
(a) administering to the subject an effective amount of the antibody or antigen binding fragment of claim 3 , wherein the antibody is configured to localize to a tumor expressing CD22 and is labeled with a radioisotope; and
(b) detecting the presence of a tumor in the subject by detecting radioactive levels emitted by the antibody or antigen binding fragment that are higher than a reference value, optionally wherein
the subject is diagnosed with or is suspected of having a CD22-associated cancer, or
the radioactive levels emitted by the antibody or antigen binding fragment are detected using positron emission tomography or single photon emission computed tomography.
14 . The method of claim 13 , further comprising administering to the subject an effective amount of an immunoconjugate comprising a radionuclide conjugated to an antibody or antigen binding fragment thereof that comprises a V H amino acid sequence selected from the group consisting of: SEQ ID NOs: 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 16; and a V L amino acid sequence selected from the group consisting of: SEQ ID NO: 21, and SEQ ID NO: 22.
15 . The method of claim 14 , wherein the radionuclide is an alpha particle-emitting isotope, a beta particle-emitting isotope, an Auger-emitter, or any combination thereof, optionally wherein the beta particle-emitting isotope is selected from the group consisting of 86 Y, 90 Y, 89 Sr, 165 Dy, 186 Re, 188 Re, 177 Lu, and 67 Cu.
16 . A method for selecting a subject for pretargeted radioimmunotherapy comprising
(a) administering to the subject an effective amount of a complex comprising a radiolabeled DOTA hapten and the bispecific antibody or antigen binding fragment of claim 5 , wherein the complex is configured to localize to CD22 expressing tumor;
(b) detecting radioactive levels emitted by the complex; and
(c) selecting the subject for pretargeted radioimmunotherapy when the radioactive levels emitted by the complex are higher than a reference value.
17 . A method for treating cancer or increasing tumor sensitivity to radiation therapy in a subject diagnosed with a CD22-associated cancer comprising administering to the subject an effective amount of a complex comprising a radiolabeled DOTA hapten and the bispecific antibody or antigen binding fragment of claim 5 , wherein the complex is configured to localize to a CD22 expressing tumor.
18 . A method for treating cancer or increasing tumor sensitivity to radiation therapy in a subject diagnosed with a CD22-associated cancer comprising
(a) administering an effective amount of the bispecific antibody or antigen binding fragment of claim 5 , wherein the bispecific antibody or antigen binding fragment is configured to localize to a CD22 expressing tumor; and
(b) administering an effective amount of a radiolabeled-DOTA hapten to the subject, wherein the radiolabeled-DOTA hapten is configured to bind to the bispecific antibody or antigen binding fragment.
19 . The method of claim 18 , further comprising administering an effective amount of a clearing agent to the subject prior to administration of the radiolabeled-DOTA hapten.