Engineered CD276 Binders for High-Specificity Cancer Targeting
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Solution Overview
Problem
Current treatments for cancer, particularly those targeting CD276+ cells, face challenges in effectively binding to CD276 polypeptides and inducing immune responses, with existing antibodies and therapies showing limitations in specificity and efficacy.
Innovation Solution
Development of binders such as antibodies, antigen binding fragments, chimeric antigen receptors (CARs), and cell engagers that specifically target CD276 polypeptides, including engineered CAR+ cells and antibody-drug conjugates (ADCs), designed to bind to CD276+ cells and induce antibody-dependent cell-mediated cytotoxicity (ADCC) or deliver drug payloads directly to cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antibodies (omburtamab and enoblituzumab) are used to target CD276, then cancer treatment is attempted, but binding specificity and efficacy are insufficient
Solution Approach 1:
The patent modifies the binding parameters of anti-CD276 antibodies by introducing humanized mouse monoclonal antibodies with engineered complementarity-determining regions (CDRs). These CDRs are designed to bind with high affinity and specificity to CD276 polypeptides, changing the binding characteristics from the original antibodies to achieve both high reliability in specificity and improved productivity in efficacy.
Solution Approach 2:
The patent creates humanized versions of mouse monoclonal antibodies by copying and adapting the CDR sequences. The humanized antibodies retain the binding specificity of the original mouse antibodies while improving efficacy through humanization, effectively copying the successful binding mechanism while optimizing for human use.
2Productivity
If conventional cancer treatments are used, then general cancer therapy is provided, but off-target effects occur and treatment precision is reduced
Solution Approach 1:
The patent applies local quality by designing antibodies with specific CDR sequences that target only CD276+ cancer cells. The antibody binding sites are engineered to recognize specific epitopes on CD276, providing localized treatment effectiveness while minimizing off-target effects on non-target cells. This specificity is achieved through the localized binding action of the engineered CDRs.
Data Source
AI summary
This document provides methods and materials involved in binding a binder (e.g., an antibody, antigen binding fragment, antibody domain, CAR, cell engager, and/or ADC) to a CD276 polypeptide. For example, binders (e.g., antibodies, antigen binding fragments, antibody domains, CARs, cell engagers, and/or ADCs) that bind to a CD276 polypeptide and methods and materials for using one or more such binding molecules to treat a mammal (e.g., a human) having cancer are provided.