Compositions and methods for modulating cellular internalization
By designing a guide-effect bispecific antibody to regulate the internalization properties of cell surface antigens, the problem of uneven internalization when targeting cancer cells was solved, and the efficacy of the antibody and ADC was improved, especially in cancer cells with uneven expression of EphA2 and ALCAM, where the killing effect was significantly enhanced.
CN113614111BActive Publication Date: 2026-07-03RGT UNIV OF CALIFORNIA
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- RGT UNIV OF CALIFORNIA
- Filing Date
- 2020-01-14
- Publication Date
- 2026-07-03
AI Technical Summary
Technical Problem
Existing therapeutic antibodies and antibody-drug conjugates (ADCs) face challenges in target selection when targeting cancer cells, as well as uneven expression and poor internalization of tumor-specific antigens, resulting in limited efficacy.
Method used
Design guide-effect bispecific antibodies to regulate cell type-selective internalization and signal transduction function retargeting by binding to specific guide antigens and effector antigens on the cell surface.
Benefits of technology
It improved the internalization efficiency and efficacy of therapeutic antibodies and ADCs in cancer cells, enhanced their killing ability against cancer cells, and showed significant effects, especially in cancer cells with uneven expression of EphA2 and ALCAM.
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Figure CN113614111B_ABST
Abstract
This document provides compositions and methods for modulating the internalization properties of cell surface molecules, such as converting non-internalized cell surface antigens into internalized cell surface antigens and converting internalized cell surface antigens into non-internalized cell surface antigens. In some embodiments, engineered antibodies are provided, each comprising an antigen-binding moiety specific to a guide antigen and another antigen-binding moiety specific to an effector antigen, wherein the internalization properties of said engineered antibody or a functional fragment thereof are determined by the relative surface density ratio of said guide antigen to said effector antigen. Recombinant cells, recombinant nucleic acids encoding such engineered antibodies, and pharmaceutical compositions containing them are also provided. This disclosure also provides methods for modulating cell internalization in cells or subjects, and methods for modulating cell type-selective signaling in subjects and / or for treating diseases.
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