CD70 CAR Binding Design for Broader Tumor Targeting
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Solution Overview
Problem
Current chimeric antigen receptor-modified T cell (CAR-T) therapies primarily target CD19 antigen on B cell tumors, limiting the effectiveness of tumor immunotherapy, and there is a need for more effective targets like CD70, which is highly expressed in various tumor tissues.
Innovation Solution
Development of a CD70-targeting chimeric antigen receptor (CD70 CAR) that includes specific antibodies and CAR molecules capable of binding to CD70, comprising heavy and light chain variable regions with defined complementarity determining regions (CDRs) and a signaling domain, for use in CAR-T cells to treat CD70-positive tumors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR-T therapy targets only CD19 antigen, then B cell tumor treatment is effective, but treatment effectiveness against other tumor types is limited
Solution Approach 1:
The patent develops CAR-T cells that can target multiple antigens including CD19, CD20, CD70, and other B-cell associated antigens. This multi-targeting approach allows a single CAR-T therapy to treat various B-cell malignancies ( CLL, SLL, MCL, DLBCL, FL, WM) beyond just CD19-positive tumors, thereby improving versatility while maintaining treatment effectiveness
2Adaptability or versatility
If new antigen targets like CD70 are developed, then adaptability to different tumors is improved, but manufacturing complexity increases
Solution Approach 1:
The patent segments the CAR structure into distinct functional domains: antigen recognition domain (targeting CD70 or other antigens), co-stimulatory domains (CD28, 4-1BB), and signaling domains. This modular segmentation allows independent optimization of each domain and facilitates the development of multiple CAR variants targeting different antigens without redesigning the entire structure, thereby managing complexity while improving adaptability
Solution Approach 2:
The patent employs different co-stimulatory domain combinations (CD28/4-1BB, CD28/CD28, 4-1BB/4-1BB) and varying CAR structures (single-chain, dual-chain, multi-specific) to optimize therapeutic effectiveness for different tumor types. By changing parameters such as co-stimulatory domain selection and antigen binding affinity, the patent achieves adaptability across multiple tumor types while maintaining manageable structural complexity through systematic variation
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The CD70 CAR enables CAR-T cells to specifically target and eliminate CD70-positive tumors, promoting cytokine release and enhancing therapeutic efficacy against cancers such as renal cell carcinoma, metastatic breast cancer, brain tumors, leukemia, and lymphoma.
Implementation Method 1
The heavy chain variable region includes a HCDR1, a HCDR2 and a HCDR3, and the light chain variable region includes a LCDR1, a LCDR2 and a LCDR3... capable of specifically binding to CD70 protein
Data Source
AI summary
A CD70 antibody and a chimeric antigen receptor (CAR) that can specifically bind to a CD70 protein. The CAR comprises a CD70 binding domain, a transmembrane domain, a costimulatory domain, and an intracellular signaling domain. Further disclosed is an application of the antibody and the CAR for treating diseases or conditions related to CD70 expression.