Human monoclonal antibodies specific for CD22
Inventors
Dimitrov, Dimiter S. • Xiao, Xiaodong • Pastan, Ira H.
Assignees
US Department of Health and Human Services
Publication Number
US-10494435-B2
Publication Date
2019-12-03
Expiration Date
2029-04-01
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Abstract
Disclosed herein are isolated human monoclonal antibodies that specifically bind human CD22 with a dissociation constant (Kd) of 25 nM or less. Nucleic acids encoding these antibodies, expression vectors including these nucleic acid molecules, and isolated host cells that express the nucleic acid molecules are also disclosed. The antibodies can be used to detect human CD22 in a sample. In some cases, CD22 is soluble CD22. Methods of diagnosing a B-cell malignancy, or confirming a B-cell malignancy diagnosis, are disclosed herein that utilize these antibodies. Methods of treating a subject with a B-cell malignancy are also disclosed.
Core Innovation
Disclosed herein are isolated human monoclonal antibodies that specifically bind human CD22 with a dissociation constant (Kd) of 25 nM or less, including examples where the Kd ranges from about 2 to about 20 nM. Nucleic acids encoding these antibodies, expression vectors comprising such nucleic acids, and isolated host cells that express these nucleic acids are also provided. Immunoconjugates comprising these human monoclonal antibodies and compositions containing these immunoconjugates are described as well. These antibodies and compositions can be used for research, diagnostic, and therapeutic purposes involving CD22.
The invention addresses the need for fully human antibodies that specifically bind CD22 with high affinity, which are useful in the diagnosis and treatment of cancer, particularly B-cell malignancies. Existing mouse monoclonal antibodies face limitations due to the human anti-murine antibody (HAMA) response, which can cause allergic reactions and accelerate antibody clearance. The production of fully human antibodies is difficult since human antigens are typically recognized as self, but this disclosure provides such antibodies with high affinity for human CD22.
Methods employing these antibodies include diagnosing or confirming a B-cell malignancy by detecting CD22, including soluble CD22, in biological samples. Additionally, methods of treating subjects diagnosed with B-cell malignancies by administering therapeutically effective amounts of these human CD22-specific monoclonal antibodies or immunoconjugates comprising these antibodies are disclosed. The antibodies can be provided in various formats, including IgG, Fab, and scFv, and can be linked to effector molecules such as toxins, for example, Pseudomonas exotoxin.
Claims Coverage
The claims cover methods of treating CD22-expressing B-cell malignancies using specific human monoclonal antibodies or immunoconjugates, and methods of diagnosing or confirming such malignancies by detecting CD22 using these antibodies. The following inventive features are extracted from the independent claims.
Human monoclonal antibody comprising specific heavy and light chain sequences
The antibody comprises a heavy chain containing amino acid residues 26-35, 53-61, and 100-113 of SEQ ID NO: 3 and a light chain containing amino acid residues 27-32, 50-52, and 89-97 of SEQ ID NO: 4.
Antibody conjugated to an agent that inhibits or kills malignant B cells for treatment
Administering a therapeutically effective amount of a monoclonal antibody conjugated to an agent (such as a toxin including Pseudomonas exotoxin) that inhibits growth or kills malignant B cells, thereby treating a subject with a CD22-expressing B-cell malignancy.
Use of antibody formats including Fab, scFv, or IgG antibody
The monoclonal antibody can be in Fab, scFv, or IgG format, including particularly the scFv format.
Immunoconjugate comprising the antibody linked to an effector molecule
Administering a therapeutically effective amount of an immunoconjugate consisting of the antibody as described above linked to an effector molecule that inhibits or kills malignant B cells, including toxins such as Pseudomonas exotoxin, for treatment of CD22-expressing B-cell malignancies.
Method of detecting or confirming CD22-expressing B-cell malignancy by antibody binding
Contacting a subject's sample with the monoclonal antibody comprising the specified heavy and light chain residues, detecting antibody binding to CD22, and determining the presence or confirming diagnosis of CD22-expressing B-cell malignancy if increased binding compared to a control sample is observed. The antibody may be directly labeled for detection.
The claims comprehensively cover methods and compositions involving human monoclonal antibodies with specified heavy and light chain sequences, their use as immunoconjugates or alone for treating B-cell malignancies expressing CD22, and methods for diagnosing or confirming such malignancies by detecting CD22 with these antibodies.
Stated Advantages
The fully human monoclonal antibodies avoid the human anti-murine antibody (HAMA) response, reducing allergic reactions and antibody clearance issues associated with mouse antibodies.
The antibodies specifically bind human CD22 with high affinity (Kd of about 25 nM or less), enabling effective diagnostic and therapeutic use.
The antibodies can be produced in various formats (IgG, Fab, scFv), providing versatility for different clinical and research applications.
Documented Applications
Detection and quantitation of soluble CD22 in biological samples for diagnosing or confirming B-cell malignancies such as non-Hodgkin's lymphoma, hairy cell leukemia, and chronic lymphocytic leukemia.
Treatment of subjects diagnosed with CD22-expressing B-cell malignancies by administering therapeutically effective amounts of human CD22-specific monoclonal antibodies or immunoconjugates comprising these antibodies, including those linked to Pseudomonas exotoxin.
Use of antibodies in diagnostic assays, e.g., sandwich ELISA and flow cytometry, to detect CD22 expression on cells or soluble CD22 in fluids for clinical evaluation.
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