Anti-CD24 compositions and uses thereof
Inventors
Liu, Yang • Zheng, Pan • FLORES, RHONDA • CHOU, HUNG-YEN • XUE, ZHIHONG • YE, PEIYING • DEVENPORT, Martin
Assignees
Children's Research Institute Children's National Medical Center • Oncoc4 Inc
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Publication Number
US-12286485-B2
Publication Date
2025-04-29
Expiration Date
Abstract
Provided herein are anti-CD24 antibodies that selectively bind human CD24 expressed in cancer cells, but not human CD24 expressed in non-cancerous cells, and the use of such antibodies in cancer therapy.
Core Innovation
The invention relates to anti-CD24 antibody compositions that preferentially bind a cancer-specific, glycan-shielded CD24 epitope. Binding is described as being blocked by glycosylation present in normal cells but not in cancer cells, thereby enabling preferential interaction with malignant cells.
The description identifies anti-CD24 antibody candidates including 3B6, an affinity-matured PP6373, and humanized H2L3/H3L3, with specified sequence identifiers. An example epitope is described as SNSGLAPN (SEQ ID NO:48), and the antibodies are presented as engineered to achieve glycan-regulated interaction with CD24 in a differential manner between normal and malignant tissue.
The disclosure also encompasses therapeutic and utility concepts supported by the compositions, including ADCC/ADCP activity, bispecific CD24×CD3 antibodies, and CAR-T or TCR use with CD24 scFv. Diagnostic use is described for malignant tissue and circulating cancer cells, including reduced reactivity to normal tissues as a functional theme of the preferential glycan-shielded epitope targeting.
Claims Coverage
The independent claim set provided here contains one independent claim (clm-00001). It defines the anti-CD24 antibody at the level of allowed heavy-chain and light-chain variable region sequence combinations, which dependent claims refine for additional structural elements and biomedical contexts.
Anti-CD24 antibody variable region sequence combinations
An anti-CD24 antibody comprising (a) a heavy chain variable region comprising the sequence set forth in SEQ ID NO: 31 or 30 and a light chain variable region comprising the sequence set forth in SEQ ID NO: 35; or (b) a heavy chain variable region from the sequence set forth in SEQ ID NO: 6 and a light chain variable region from the sequence set forth in SEQ ID NO: 16.
Anti-CD24 antibody with human immunoglobulin constant (Fc) region
The anti-CD24 antibody additionally includes a human immunoglobulin constant (Fc) region.
Specific SEQ ID pairing for heavy and light chain variable regions
The anti-CD24 antibody includes a heavy chain variable region with the sequence of SEQ ID NO: 31 and a light chain variable region with the sequence of SEQ ID NO: 35.
Cancer growth reduction in a patient with CD24-expressing cancer cells
A method reduces cancer growth in a patient by administering an anti-CD24 antibody (per the anti-CD24 antibody of the independent claim) where the cancer cells express CD24.
Bispecific antibody using anti-CD24 first domain and specified second domain sequence sets
A bispecific antibody includes an anti-CD24 first antibody domain and a second antibody (or antigen-binding fragment) domain, where the bi-specific antibody sequence corresponds to SEQ ID NOs: 17 and 18 or to sequences within SEQ ID NOs: 23-27 and 37-41.
Chimeric antigen receptor containing an anti-CD24 single-chain antibody
A chimeric antigen receptor includes a single-chain antibody containing the anti-CD24 antibody described in the independent claim.
Across the provided claim scope, the central inventive coverage is an anti-CD24 antibody defined by specific heavy/light variable region sequence combinations, optionally including an Fc region. Dependent claim refinements include specified SEQ ID pairings, methods to reduce cancer growth in patients with CD24-expressing cancer cells, bispecific CD24 constructs with defined sequence sets, and a CAR incorporating an anti-CD24 single-chain antibody.
Stated Advantages
Preferentially binds a cancer-specific, glycan-shielded CD24 epitope compared with normal cells, with binding blocked by glycosylation present in normal cells but not in cancer cells.
Reduced reactivity to normal tissues.
Enables ADCC/ADCP therapeutic activity as described in the disclosure.
Supports therapeutic formats including bispecific CD24×CD3 antibodies and CAR-T/TCR anti-tumor activity as described in the disclosure.
Documented Applications
Therapeutic use: reducing cancer growth in a patient by administering the anti-CD24 antibody where cancer cells express CD24.
Bispecific antibody format: a bispecific antibody including an anti-CD24 first antibody domain and a second antibody (or antigen-binding fragment) domain with specified sequence sets.
Immunotherapy construct: chimeric antigen receptor including an anti-CD24 single-chain antibody.
Diagnostic/utility concept: diagnosing malignant tissue and circulating cancer cells.
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