DuoCAR T-Cell Compositions for Persistent Multi-Target Cancer Therapy
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Solution Overview
Problem
Current challenges in cancer treatment using chimeric antigen receptors (CARs) include limited in vivo expansion of CAR+ T cells, rapid disappearance of cells after infusion, disappointing clinical activity, and the undue length of time between diagnosis and treatment, along with the difficulty in finding cancer-specific targets that spare normal tissues.
Innovation Solution
The development of compositions comprising at least two vectors encoding functional DuoCARs, which express two or more non-identical binding domains covalently linked to transmembrane and intracellular signaling motifs, to generate patient-specific anti-tumor lymphocyte populations for targeted cancer therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CAR therapy is used, then cancer treatment is provided, but limited in vivo expansion of CAR+ T cells occurs and cells disappear rapidly after infusion
Solution Approach 1:
The patent divides the CAR signaling into two separate components: a first CAR with a first signaling motif and a second CAR with a second signaling motif. This segmentation allows independent optimization of each CAR's function, where one CAR provides antigen recognition and the other provides costimulatory signals, thereby improving T cell persistence and expansion in vivo.
Solution Approach 2:
The patent combines two different CARs (first CAR and second CAR) within the same T cell population, where each CAR expresses different binding domains and signaling motifs. This merging of functional elements enables synergistic effects that improve both tumor targeting and T cell persistence, resolving the contradiction between cancer treatment efficacy and cell longevity.
2Reliability
If conventional CAR therapy is used, then cancer treatment is provided, but disappointing clinical activity is observed
Solution Approach 1:
By segmenting the CAR function into two separate CARs with specialized roles (one for antigen binding, one for signaling), the patent improves the reliability of clinical activity. Each CAR can be optimized for its specific function, leading to more effective T cell activation and tumor response.
Solution Approach 2:
The patent changes the parameters of CAR therapy by introducing diversity in binding domain specificity and signaling motif combinations. This parameter change enables better matching between T cell receptors and tumor antigens, improving both clinical activity and tumor response rate.
3Measurement precision
If time is taken between biopsy and treatment, then diagnostic accuracy is improved, but tumor grows unimpeded and disease progresses
Solution Approach 1:
The patent enables preliminary action by allowing rapid generation of patient-specific CAR T cells through standardized protocols. The modular CAR design facilitates quick customization based on biopsy results, reducing the time between diagnosis and treatment while maintaining diagnostic accuracy.
4Measurement precision
If cancer-specific targets are sought, then treatment specificity is improved, but difficulty in finding targets that spare normal tissues occurs
Solution Approach 1:
The patent applies local quality by enabling selection of CARs with binding domains specific to particular tumor antigens. Different CARs can be designed to target different antigens expressed on tumor cells but not on normal tissues, thereby achieving high target specificity while minimizing harm to normal tissues.
Data Source
AI summary
Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.