Anti-CD72 CARs for B Cell Lymphoma Relapse Prevention
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Solution Overview
Problem
Antigen escape or downregulation is a mechanism for relapse from CAR T-cell therapy, as cancer cells can lose detectable antigens like CD19 or CD22, making it challenging to target residual leukemic/lymphoma blasts.
Innovation Solution
Development of CD72-specific chimeric antigen receptors (CARs) that target CD72, a C-type lectin receptor with restricted expression on B cells and myeloid blasts, allowing simultaneous targeting of multiple antigens to overcome antigen escape.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR T-cell therapy targets a single antigen (e.g., CD19 or CD22), then the therapy shows initial effectiveness, but cancer cells can escape through antigen downregulation or loss, leading to relapse
Solution Approach 1:
The patent creates CAR T-cells that simultaneously target multiple antigens (CD19, CD22, and CD72) by co-expressing multiple CAR constructs. This multi-functional approach ensures that even if one antigen is downregulated or lost, the T-cells can still recognize and eliminate cancer cells through alternative antigens, thereby preventing relapse and improving therapeutic durability
2Productivity
If CAR T-cells apply strong immune pressure to eliminate cancer cells, then tumor burden decreases, but cancer cells escape by downregulating or losing target antigens
Solution Approach 1:
The patent preemptively addresses antigen escape by designing CAR T-cells with multiple targeting capabilities before treatment begins. By pre-equipping the T-cells with the ability to recognize multiple antigens (CD19, CD22, CD72), the system prevents cancer cells from escaping through antigen loss, as the T-cells can immediately switch to alternative targets without requiring additional immune pressure or time
3Reliability
If the therapy targets multiple antigens simultaneously, then resistance to relapse is reduced, but the complexity of the CAR construct increases
Solution Approach 1:
The patent divides the multi-targeting CAR system into separate modular CAR constructs, each targeting a specific antigen (CD19 CAR, CD22 CAR, CD72 CAR). These modular units can be co-expressed in the same T-cell through multiple viral transductions, allowing the system to achieve multi-antigen targeting while maintaining the simplicity and functionality of individual CAR components
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 CD72 CARs effectively target and eliminate CD72-expressing cancer cells, including B cell lymphomas and leukemias, even after relapse, providing a durable and long-term therapeutic response.
Implementation Method 1
a binding domain that specifically binds to CD72
Data Source
AI summary
The present disclosure relates to compositions and methods comprising anti-CD72 chimeric antigen receptors, host cells modified to include anti-CD72 chimeric antigen receptor molecules. The provided compositions, methods, and uses include those for combination therapies involving administration of a chimeric engulfment receptor or chimeric Tim receptor, such as immune cells engineered to co-express both the anti-CD72 chimeric antigen receptor and the chimeric engulfment receptor or chimeric Tim receptor.