SSEA4-Specific CAR T Cells for Ovarian Cancer Treatment
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for ovarian cancer, renal cell carcinoma, and triple negative breast cancer (TNBC) have limited therapeutic options and are associated with poor efficacy and severe side effects, with chemotherapy resistance leading to tumor recurrence and metastasis in many patients.
Innovation Solution
Engineering T cells to express a chimeric antigen receptor (CAR) specific for the SSEA4 antigen, which allows targeted recognition and killing of SSEA4-positive cancer cells, utilizing a CAR comprising a specific antigen binding domain, transmembrane domain, and intracellular signaling domain to induce cytokine secretion and cytotoxic activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemotherapy is used to treat ovarian cancer, renal cell carcinoma, and TNBC, then initial tumor response is achieved, but chemotherapy resistance develops leading to tumor recurrence and metastasis
Solution Approach 1:
Instead of using conventional chemotherapy that kills dividing cells non-specifically, the patent inverts the approach by using genetically modified T cells that actively seek out and kill cancer cells expressing SSEA4 antigen through specific recognition and targeted cytotoxicity, thereby overcoming chemotherapy resistance
Solution Approach 2:
The patent introduces an intermediary system - genetically modified T cells expressing chimeric antigen receptors (CARs) specific for SSEA4 - that mediates the killing of cancer cells. This intermediary approach bypasses the resistance mechanisms that block conventional chemotherapy from effectively eliminating residual cancer cells
2Productivity
If conventional chemotherapy is used for systemic therapy, then some tumor regression is achieved, but severe side effects occur and efficacy remains poor
Solution Approach 1:
The patent applies local quality by endowing T cells with specific local functionality through CAR expression that enables them to recognize and kill only cancer cells expressing SSEA4 antigen, while leaving healthy cells unaffected. This localized targeted action eliminates the non-specific toxicity that causes severe side effects in conventional chemotherapy
Solution Approach 2:
The patent changes the fundamental parameter of cancer cell recognition from non-specific chemical vulnerability to specific antigen recognition. By modifying T cells to express CARs that specifically bind SSEA4, the system achieves selective tumor regression without the collateral damage to healthy tissues that causes severe side effects
3Reliability
If T cells are engineered to express SSEA4-specific CAR, then targeted killing of cancer cells is achieved, but device complexity increases
Solution Approach 1:
The patent merges multiple functional domains into a single chimeric antigen receptor protein structure, combining the antigen-binding scFv domain, transmembrane domain, and intracellular signaling domains (CD28 and CD3ζ) into one integrated CAR molecule that can be expressed by genetically modified T cells, thereby achieving targeted cancer cell killing through a unified construct
Data Source
Figure 1
Figure 2A
Figure 2B
AI summary
The present invention provides chimeric antigen receptors (CARs) comprising an antigen binding domain specific for SSEA4, a population of engineered cells expressing said CARs, and a pharmaceutical composition comprising said genetically modified cells expressing said CARs. The pharmaceutical composition may be for use of the treatment of cancer in a subject suffering from cancer, wherein at least a subpopulation of the cancerous cells of said cancer expresses SSEA4.