Human monoclonal antibodies specific for CD22

Inventors

Dimitrov, Dimiter S. • Xiao, Xiaodong • Pastan, Ira H.

Assignees

US Department of Health and Human Services

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

This invention relates to isolated human monoclonal antibodies that specifically bind human CD22 with a dissociation constant (Kd) of 25 nM or less. The disclosure includes nucleic acids encoding these antibodies, expression vectors incorporating these nucleic acids, and isolated host cells expressing the nucleic acids. These antibodies can detect human CD22 in samples, including soluble CD22, and are useful for diagnosing, confirming diagnosis, and treating B-cell malignancies.

The background identifies CD22 as a B-cell surface sialoglycoprotein involved in B-cell activation and adhesion, expressed in mature B cells and notably on 60-70% of B-cell lymphomas and leukemias. CD22's expression in B-cell malignancies makes it a target for immunotherapy. Existing mouse monoclonal antibodies elicit human anti-murine antibody (HAMA) responses, causing allergic reactions and increased antibody clearance, limiting their clinical utility. Therefore, there is a need for fully human antibodies that specifically bind CD22 with high affinity to improve diagnosis and treatment of B-cell malignancies, despite the difficulty in generating such fully human antibodies due to self-tolerance.

The disclosed fully human monoclonal antibodies bind CD22 with high affinity, with Kd values from about 2 nM to about 25 nM, and show specificity towards native and soluble CD22. The disclosure provides compositions including these human monoclonal antibodies, methods of diagnosing or confirming B-cell malignancies based on detecting CD22 binding, and methods of treating subjects with B-cell malignancies by administering therapeutically effective amounts of these antibodies or immunoconjugates thereof. Immunoconjugates comprising the antibodies linked to therapeutic agents, such as toxins, are also included. The antibodies avoid HAMA responses because they are fully human, providing clinical advantages over murine or humanized antibodies.

Claims Coverage

The patent claims cover methods of treating and diagnosing CD22-expressing B-cell malignancies using fully human monoclonal antibodies with specified sequences and conjugates, with multiple inventive features related to antibody composition, conjugation, and diagnostic application.

The claims establish the invention's scope covering specific human monoclonal antibodies targeting CD22 with defined sequence residues, their conjugation to therapeutic agents especially toxins, multiple antibody formats, and diagnostic methods based on detecting CD22 binding for B-cell malignancies.

Stated Advantages

Documented Applications