MAGE A4 Targeted TCR-Modified T Cells for Cancer Therapy
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Solution Overview
Problem
Current treatments for head and neck or lung cancer often result in significant toxicity and side effects, and there is a need for a cancer-specific therapy that can effectively treat intermediate or late-stage cancers, particularly after primary therapy or surgery, while minimizing systemic toxicity and tissue damage.
Innovation Solution
Administering modified immunoresponsive cells expressing or presenting a heterologous T-cell receptor (TCR) or chimeric antigen receptor (CAR) that binds specifically to the MAGE A4 antigenic peptide GVYDGREHTV, which is naturally processed and isolated from head and neck and lung carcinoma lines, to target and treat cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional chemotherapy or radiotherapy is used to treat head and neck or lung cancer, then tumor growth is reduced, but significant toxicity and side effects occur
Solution Approach 1:
The patent segments the treatment approach by using genetically modified T-cells that express heterologous TCRs or CARs with specific affinity for MAGE A4 antigen. This allows the immune system to be divided into targeted components that specifically recognize and attack cancer cells expressing MAGE A4, rather than affecting all rapidly dividing cells as conventional chemotherapy does. The segmentation principle is applied by creating a specialized subset of immune cells with enhanced, antigen-specific recognition capability.
Solution Approach 2:
The patent applies local quality by engineering T-cells with modified receptors that have enhanced binding affinity specifically for MAGE A4 antigen presented on cancer cells. The heterologous TCRs or CARs are designed to recognize MAGE A4 with higher specificity and affinity than endogenous T-cells, creating a localized enhancement of immune recognition at the cancer cell surface without affecting normal tissues. This targeted approach concentrates therapeutic effect where needed while sparing healthy tissues.
2Reliability
If surgery is used for early-stage cancer, then cure rates improve, but patients with advanced cancer require additional therapies that increase toxicity
Solution Approach 1:
The patent applies preliminary action by genetically modifying T-cells ex vivo before administration, equipping them with heterologous TCRs or CARs that target MAGE A4 antigen. This preliminary engineering of immune cells creates a pre-activated, cancer-specific therapeutic agent that can be administered systemically. The preliminary action of genetic modification allows the cells to be prepared with enhanced anti-cancer activity before encountering the tumor, reducing the need for multiple sequential therapies.
Solution Approach 2:
The patent uses genetically modified T-cells as an intermediary between the patient's immune system and the cancer cells. These engineered cells serve as mediators that bridge the gap between natural immune recognition and effective anti-tumor response. The heterologous TCRs or CARs on the T-cell surface act as intermediaries that specifically bind to MAGE A4 on cancer cells, translating antigen recognition into targeted cytotoxic activity without requiring direct contact between conventional immune cells and tumor cells.
3Object-affected harmful factors
If immunotherapy is used to enhance cancer-specific response, then side effects are minimized, but treatment efficacy for intermediate or late-stage cancer needs improvement
Solution Approach 1:
The patent applies parameter changes by modifying the binding affinity parameters of T-cell receptors through genetic engineering. The heterologous TCRs or CARs are designed with altered affinity constants for MAGE A4 antigen compared to endogenous T-cells. This parameter change in receptor affinity enhances the sensitivity and effectiveness of immune recognition for cancer cells, allowing effective treatment of intermediate or late-stage disease while maintaining the safety profile of immunotherapy by avoiding non-specific activation.
Data Source
AI summary
The present invention relates to a method of treating, preventing or delaying the progression of cancer and/or tumour in a subject comprising administering to the subject a treatment regimen comprising an effective amount of modified immunoresponsive cells expressing or presenting a heterologous T-cell receptor (TCR) having the property of binding to MAGE A4