Dual-Target CAR/TCR Binding Motifs Against CD19 and CD20 Evasion
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Solution Overview
Problem
Current T cell therapies for targeting and killing cancer cells face challenges due to cancer cells employing mechanisms to evade immune cells, necessitating improved chimeric antigen receptors (CARs) and engineered T cell receptors (TCRs) that can effectively bind to specific tumor antigens.
Innovation Solution
Development of antigen binding systems, including chimeric antigen receptors (CARs) with specific heavy and light chain complementarity determining regions (CDRs) that target CD20 and CD19 antigens, enhancing the ability of T cells to recognize and destroy cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current T cell therapies are used to target cancer cells, then cancer cells can be killed, but cancer cells employ mechanisms to evade immune cells reducing therapy effectiveness
Solution Approach 1:
The patent applies parameter changes by modifying the binding characteristics of the CAR through specific CDR sequences. The engineered CDRs (SEQ ID NOs: 1-22) are designed to bind CD20 with optimized affinity and specificity parameters, overcoming cancer cell evasion mechanisms that exploit weaker or non-specific binding of conventional CARs.
Solution Approach 2:
The patent employs composite materials by creating a chimeric antigen receptor that combines antibody-derived CDR binding domains with T cell receptor signaling components. This composite structure integrates the specific antigen recognition capability of antibodies (anti-CD20 CDRs) with the cytotoxic functionality of T cells, resulting in a hybrid receptor that overcomes evasion mechanisms.
2Reliability
If T cells are engineered to express CARs with binding domains, then ability to target specific cancer cells is increased, but complexity of the therapeutic construct increases
Solution Approach 1:
The patent applies the extraction principle by isolating and utilizing only the essential antigen-binding CDR sequences from antibodies (SEQ ID NOs: 1-22) and integrating them directly into the CAR structure. This extracts the core functionality needed for specific CD20 recognition while eliminating unnecessary portions of the antibody structure, thereby reducing overall construct complexity.
Solution Approach 2:
The patent implements universality by designing a modular CAR construct where the anti-CD20 CDR binding domain can be combined with various T cell signaling domains and transmembrane regions. This universal platform allows the same CDR sequences to be integrated into different CAR architectures, reducing the need to redesign entire constructs for different applications.
3Reliability
If conventional CARs are used, then T cells can recognize cancer cells, but specificity and efficacy in killing cancer cells is insufficient
Solution Approach 1:
The patent applies local quality by optimizing the specific CDR regions (SEQ ID NOs: 1-22) that directly contact the CD20 antigen. These localized binding domains are engineered with precise amino acid sequences to maximize affinity and specificity for CD20, while the rest of the CAR structure maintains standard functional domains. This localized optimization enhances killing efficacy without requiring complete redesign of the entire receptor.
Data Source
AI summary
Provided is a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising one or more of the antigen binding motifs disclosed herein. Aspects of the disclosure relate to a polynucleotide encoding a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising one or more of the antigen binding motifs. Provided are antibodies and antigen binding systems that comprise a binding motif that binds CD20 and optionally a binding motif that binds CD19, and methods of producing and using the same. Antibodies and antigen binding systems of the present disclosure comprise CARs that comprise an anti-CD20 binding motif and an anti-CD19 binding motif. Provided are compositions, such as antibodies and CARs that are or comprise an anti-CD20/anti-CD19 antigen binding system of the present disclosure, and cell therapies comprising the same, are useful, e.g., in the treatment of cancer.