Multi-Cytokine Tumor Therapy for Immunosuppressive Microenvironments
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Solution Overview
Problem
Current immunotherapies for tumors, such as CAR-T and immune checkpoint therapy, face limitations due to the dense immunosuppressive tumor microenvironment, leading to poor efficacy in treating solid tumors, with existing cytokine combinations failing to achieve satisfactory results.
Innovation Solution
A cytokine combination of at least three cytokines, including IL12, GMCSF, FLT3L, IL2, IL15, IL21, and IL7, is administered topically to activate the immune system within the tumor, disrupt the immunosuppressive microenvironment, and stimulate an effective immune response against tumors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If CAR-T immunotherapy is used to treat tumors, then tumor cells can be identified and killed more accurately, but the therapy fails to achieve ideal effect due to poor penetration into solid tumors and suppression in the tumor microenvironment
Solution Approach 1:
The patent combines multiple cytokines (IL-12, GM-CSF, FLT3-L, IL-2, IL-15, IL-21, IL-7) into a synergistic combination therapy that simultaneously activates multiple immune cell types including CAR-T cells, NK cells, and macrophages. This multi-component approach overcomes the limitation of single-agent CAR-T therapy by creating a comprehensive immune activation effect that can penetrate and survive in the tumor microenvironment more effectively.
Solution Approach 2:
The patent uses a composite cytokine formulation containing multiple immunostimulatory proteins working together. This composite biological material creates a synergistic effect where the combination of cytokines produces greater immune activation than individual cytokines alone, enabling better penetration through the immunosuppressive tumor microenvironment and sustained therapeutic effect.
2Object-generated harmful factors
If immune checkpoint therapy is used to block immunosuppressive signal pathways, then T cell functions can be reactivated, but the low response rate (20-30%) indicates insufficient ability to eliminate solid tumors
Solution Approach 1:
The patent merges immune checkpoint inhibition with multiple cytokine therapies (IL-12, GM-CSF, FLT3-L, IL-2, IL-15, IL-21, IL-7) to create a combination that simultaneously blocks immunosuppressive pathways and actively stimulates multiple immune cell types. This synergistic combination overcomes the limited response rate of checkpoint therapy alone by providing both negative signal blocking and positive immune activation.
Solution Approach 2:
The cytokine combination acts as intermediary substances that mediate between the blocked immune checkpoint pathways and the tumor cells. The cytokines serve as signaling molecules that bridge the gap by activating immune cells to directly attack tumor cells, providing an additional mechanism beyond simple pathway blocking to achieve tumor elimination.
3Productivity
If existing cytokine combinations are used to treat tumors, then some immune activation is achieved, but fully satisfactory results have not been shown
Solution Approach 1:
The patent combines seven different cytokines (IL-12, GM-CSF, FLT3-L, IL-2, IL-15, IL-21, IL-7) in a specific formulation that targets multiple immune cell types simultaneously. This comprehensive combination addresses the insufficiency of existing single or dual cytokine therapies by creating a synergistic network that activates innate immunity, acquired immunity, and tumor-specific immunity all at once, achieving fully satisfactory therapeutic results.
Data Source
AI summary
Provided is a cytokine combination useful for treating a tumor and/or preventing recurrence or metastasis of the tumor. The cytokine combination with at least three cytokines selected from the following groups: interleukin 12 (IL12) or a functional variant thereof, granulocyte-macrophage colony-stimulating factor (GMCSF) or a functional variant thereof, FMS-like tyrosine kinase 3 ligand (FLT3L) or a functional variant thereof, interleukin 2 (IL2) or a functional variant thereof, interleukin 15 (IL15) or a functional variant thereof, interleukin 21 (IL21) or a functional variant thereof, and interleukin 7 (IL7) or a functional variant thereof. Also provided is a nucleic acid molecule encoding the cytokine combination and a vector thereof, a cell, a pharmaceutical composition, and a application thereof for the manufacture of a drug for treating the tumor and/or preventing recurrence or metastasis of the tumor.