CAR T-Cell Engineering with RIAD Polypeptide for Enhanced Efficacy
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Solution Overview
Problem
Current cancer therapies, such as adoptive cell transfer with autologous T-cells transduced with Chimeric Antigen Receptors (CARs), face limitations in effectively targeting a broad range of tumor antigens and inducing sustained immune responses.
Innovation Solution
Engineering immune effector cells, like T cells and NK cells, to express a CAR polypeptide that includes an antigen binding domain, a transmembrane domain, and an intracellular signaling domain, specifically binding to various tumor antigens and incorporating a RIAD or Ezrin polypeptide to enhance therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune effector cells are engineered to express CAR polypeptide alone, then the cells can recognize tumor antigens, but the therapeutic efficacy and sustained immune response are limited
Solution Approach 1:
The patent combines CAR polypeptide and RIAD/Ezrin polypeptide into a single engineered immune effector cell. The CAR component provides tumor antigen recognition and binding, while the RIAD/Ezrin component enhances cytotoxic activity and immune response sustainment. This merging of two functional elements into one cell system resolves the contradiction by achieving both reliable therapeutic efficacy and enhanced adaptability against diverse tumor antigens.
Solution Approach 2:
The engineered immune effector cell functions as a composite biological system, integrating two distinct polypeptide components (CAR and RIAD/Ezrin) with complementary functions. The CAR domain targets specific tumor antigens while the RIAD/Ezrin domain provides enhanced effector functions, creating a composite cell therapy product that overcomes the limitations of single-component approaches.
2Reliability
If immune effector cells are engineered with multiple polypeptides to enhance efficacy, then therapeutic outcome improves, but the complexity of cell engineering increases
Solution Approach 1:
The patent divides the enhanced immune effector cell into two functional segments: the CAR polypeptide segment responsible for antigen recognition and binding, and the RIAD/Ezrin polypeptide segment responsible for enhanced cytotoxicity and sustained response. This segmentation allows for modular design and construction, where each segment can be independently optimized and then combined, thereby managing the complexity of engineering while achieving superior therapeutic outcomes.
3Productivity
If CAR polypeptide is used to target specific tumor antigens, then cancer cells can be killed, but the ability to induce sustained immune response is insufficient
Solution Approach 1:
The patent incorporates RIAD/Ezrin polypeptide into the engineered immune effector cells before administration to the patient. This preliminary action equips the cells with enhanced cytotoxic machinery and immune activation capabilities in advance, so that upon encountering tumor cells, they can immediately execute sustained killing and maintain prolonged immune response without requiring additional external stimulation during the initial therapeutic phase.
Data Source
AI summary
The invention provides compositions and methods for treating diseases associated with expression of a cancer associated antigen as described herein. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen as described herein, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen as described herein.