CD99L2 Backbone CAR-T Cells Solid Tumor Efficacy
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Solution Overview
Problem
Current CAR-T cell therapies face challenges in effectively targeting and eliminating solid tumors due to the immunosuppressive tumor microenvironment, which limits their therapeutic efficacy compared to hematologic malignancies.
Innovation Solution
The development of a novel chimeric antigen receptor (CAR) using a CD99L2-derived extracellular and transmembrane domain as the backbone, enhancing T cell activation and antitumor efficacy by overcoming the immunosuppressive barriers in solid tumors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CD8 backbone CAR-T cells are used, then the CAR-T cells can be easily manufactured and show effectiveness in hematologic malignancies, but they exhibit limited antitumor efficacy in solid tumors due to the immunosuppressive tumor microenvironment
Solution Approach 1:
The patent changes the backbone structure parameter of the CAR from conventional CD8 to CD99L2-derived backbone. This structural parameter change confers enhanced functionality to the CAR-T cells, enabling them to overcome the immunosuppressive tumor microenvironment and significantly improve antitumor efficacy in solid tumors while maintaining manufacturability
Solution Approach 2:
The patent creates a composite CAR structure by combining the antigen recognition domain with the CD99L2-derived backbone and signaling domains. This composite design integrates the tumor-targeting capability with the enhanced activation and persistence properties provided by the CD99L2 backbone, resulting in superior therapeutic outcomes
2Reliability
If the CAR backbone structure is modified to enhance T cell activation, then antitumor efficacy is improved, but the complexity of CAR design and manufacturing increases
Solution Approach 1:
The patent modifies the backbone structure parameter of the CAR by using CD99L2-derived extracellular and transmembrane domains combined with specific signaling domains. This parameter change enhances T cell activation function and antitumor efficacy while maintaining a manageable level of design complexity through systematic domain selection
Data Source
AI summary
The present invention relates to a novel chimeric antigen receptor comprising a CD99L2 region, which is known to play a key role in cell adhesion and migration, as a backbone of the chimeric antigen receptor, an immune cell comprising the same, and the uses thereof. CD99L2-based CAR-T cells exhibit enhanced T-cell activity and tumor treatment efficiency compared to conventional CAR-T cells, and thus can be useful in immune cell therapy for the treatment of cancer.