CAR-T Cell Dosing for Solid Tumor Efficacy
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Solution Overview
Problem
Current CAR-T cell therapy has limited effectiveness in treating solid tumors due to the tumor microenvironment's protective mechanisms, which hinder the activation and efficacy of immune effector cells.
Innovation Solution
Administering immune effector cells expressing a chimeric antigen receptor (CAR) specifically recognizing CLD18, with controlled dosing and timing, including multiple doses, to enhance their killing capacity and persistence in the tumor microenvironment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR-T cell therapy is applied to treat solid tumors, then anti-tumor capability is improved, but therapeutic efficacy is limited due to tumor microenvironment protective mechanisms
Solution Approach 1:
The patent modifies the CAR-T cell therapy approach by changing key parameters: using autologous T cells instead of allogeneic cells, optimizing dosing parameters (first dose of 1-10×10^6 cells/kg, second dose of 1-10×10^6 cells/kg at 2-12 weeks later), and adjusting timing parameters for multiple doses to overcome tumor microenvironment protective mechanisms and improve therapeutic efficacy in solid tumors
2Productivity
If multiple doses of immune effector cells are administered, then anti-tumor effects are enhanced, but treatment complexity increases
Solution Approach 1:
The patent divides the total treatment into segmented doses: a first dose of 1-10×10^6 cells/kg administered initially, and a second dose of 1-10×10^6 cells/kg administered 2-12 weeks later. This segmentation allows the immune effector cells to persist and accumulate anti-tumor effects while managing treatment complexity through defined dosing intervals
Solution Approach 2:
The patent ensures continuity of useful action by scheduling a second dose 2-12 weeks after the first dose, maintaining therapeutic pressure on the tumor while allowing for immune system recovery and reduction of acute side effects between doses
3Power
If high dose of immune effector cells is administered, then killing capacity is improved, but cytokine release syndrome and neurotoxicity increase
Solution Approach 1:
The patent applies partial action by using moderate doses (1-10×10^6 cells/kg per dose) rather than extremely high doses, achieving sufficient anti-tumor killing capacity while minimizing harmful effects such as cytokine release syndrome and neurotoxicity that are associated with excessive dosing
Solution Approach 2:
The patent implements periodic action by spacing doses 2-12 weeks apart, allowing the immune system to recover and clear cytokines between administrations, thereby reducing the risk of severe cytokine release syndrome and neurotoxicity while maintaining cumulative anti-tumor effect
Data Source
AI summary
Provided in the present invention are a composition of immune effector cells and a treatment kit including the composition of immune effector cells, wherein the composition of immune effector cells comprises an initial dose of immune effector cells and a subsequent dose of immune effector cells.