Chemotherapy-Resistant Immune Cell Compositions for Cancer Immunotherapy
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Solution Overview
Problem
Current cancer treatments, particularly for late-stage and metastatic cancers, face challenges due to non-specific toxicity of chemotherapy agents, downregulation of immune response by tumor cells, and resistance to immunotherapies, leading to transient responses and low survival rates.
Innovation Solution
Combination therapies involving genetically modified cytotoxic immune cells resistant to chemotherapeutic agents, administered with immune checkpoint inhibitors, to enhance immune response and overcome chemotherapy-induced toxicities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If chemotherapy agents are used to treat cancer, then tumor cells are killed, but immunocompetent cells are damaged and immune response is suppressed
Solution Approach 1:
The patent segments the treatment approach by separating chemotherapy administration from immune cell therapy administration. Chemotherapy is given first to reduce tumor burden, followed by administration of genetically modified immunocompetent cells that are resistant to chemotherapy. This temporal and functional segmentation allows each treatment to work optimally without interfering with the other.
Solution Approach 2:
The patent introduces genetically modified immunocompetent cells as an intermediary between chemotherapy and the tumor. These cells are engineered to be resistant to chemotherapy agents while maintaining their ability to recognize and kill tumor cells. They act as a bridge that allows chemotherapy to effectively reduce tumor burden while preserving immune function for subsequent anti-tumor activity.
2Reliability
If immune checkpoint inhibitors are used to enhance immune response, then anti-tumor immunity is improved, but tumor cells can evade through downregulation of MHC-class I and immune checkpoint molecules
Solution Approach 1:
The patent applies preliminary action by first administering chemotherapy to reduce tumor burden and alter the tumor microenvironment before administering immune checkpoint inhibitors. This preparatory step makes the tumor more susceptible to immune attack by reducing immunosuppressive factors and increasing the expression of immune target antigens, thereby enhancing the effectiveness of subsequent immune checkpoint inhibition.
Solution Approach 2:
The patent utilizes parameter changes by modifying the expression levels of immune checkpoint molecules and MHC-class I on tumor cells through chemotherapy pretreatment. This changes the immunogenic parameters of the tumor, making it more visible and vulnerable to immune detection and attack, thereby overcoming the tumor's adaptive evasion mechanisms.
3Productivity
If combination therapy is used to improve treatment outcomes, then anti-neoplastic efficacy is enhanced, but treatment complexity and toxicity management increase
Solution Approach 1:
The patent implements periodic action through a structured sequential treatment regimen: chemotherapy is administered in cycles to reduce tumor burden, followed by a specific interval for administering genetically modified immunocompetent cells and immune checkpoint inhibitors. This periodic, phased approach allows for manageable toxicity monitoring and reduces treatment complexity compared to simultaneous multi-agent administration.
Data Source
AI summary
The present invention provides compositions and methods for combination therapy comprising administering to a patient in need thereof, drug-resistant immunotherapy, immune checkpoint inhibitors, and chemotherapy for the treatment of cancer.