CAR T Cells with 4-1BB Domain for Ovarian Cancer
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Solution Overview
Problem
Current therapeutic approaches for ovarian cancer, including intraperitoneal chemotherapy and radiation therapy, are ineffective for advanced stages, and there is a need for novel modalities to enhance anti-tumor immunity.
Innovation Solution
Development of genetically modified T cells expressing a chimeric antigen receptor (CAR) comprising an α-folate receptor (FRα) binding domain and a 4-1BB costimulatory domain, which are administered to patients to stimulate a targeted immune response against ovarian cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If intraperitoneal chemotherapy is used as standard treatment, then initial response is achieved, but patients ultimately relapse and become incurable
Solution Approach 1:
The patent changes the fundamental parameter of treatment modality from conventional chemotherapy to adoptive cell transfer therapy. By genetically modifying T cells to express chimeric antigen receptors specific to ovarian cancer antigens, the treatment achieves both initial response and sustained long-term control, overcoming the relapse limitation of traditional chemotherapy
Solution Approach 2:
The patent implements self-service through the use of autologous T cells that are harvested from the patient, genetically modified ex vivo, and reinfused. These modified T cells autonomously recognize and attack tumor cells expressing the target antigen, providing sustained anti-tumor immunity without requiring continuous external intervention
2Measurement precision
If radiation therapy is delivered to advanced stages, then tumor targeting is achieved, but high dose cannot be safely delivered due to vital organs in radiation field
Solution Approach 1:
The patent uses genetically modified T cells as living intermediaries that specifically recognize tumor antigens and mediate targeted killing. This biological mediator approach achieves precise tumor targeting through antigen-specific recognition while inherently sparing vital organs, as the modified T cells only attack cells expressing the target antigen
Solution Approach 2:
The patent replaces the mechanical radiation delivery system with a biological system consisting of adoptively transferred T cells. This substitution eliminates the need for external radiation delivery while achieving comparable or superior tumor targeting through the biological specificity of antigen-receptor interactions
3Productivity
If surgical therapy is performed, then tumor removal is achieved, but it is not effective for advanced stages
Solution Approach 1:
The patent creates a universal treatment approach that can be applied across different stages of ovarian cancer. The adoptive cell transfer therapy with antigen-specific T cells provides both curative potential for early stages and palliative benefit for advanced stages, unlike surgery which is limited to resectable disease
Solution Approach 2:
The patent introduces dynamic adaptability by using genetically modified T cells that can actively seek out and respond to tumor cells throughout the body. Unlike static surgical removal limited to accessible tumors, the modified T cells dynamically navigate the body, recognize antigen-positive cells, and provide ongoing immune surveillance and attack
Data Source
AI summary
The invention provides compositions and methods for treating ovarian cancer. Specifically, the invention relates to administering a genetically modified T cell having α-folate receptor (FRα) binding domain and 4-1BB (CD137) costimulatory domain to treat ovarian cancer.