CAR-T and APC Dual-Cell Therapy for Solid Tumor Activation
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Solution Overview
Problem
Conventional CAR-T therapy is ineffective in treating solid tumors due to lack of significant activation of the inflammatory response and insufficient recruitment or activation of antigen-presenting cells (APCs) at the tumor site.
Innovation Solution
The use of isolated nucleic acids encoding binding molecules, such as chimeric antigen receptors (CAR) or modified T cell receptors (TCR), and therapeutic agents like inflammatory cytokines or fusion proteins, to modulate T cell gene expression and enhance their proliferative and inhibitory capacities, thereby recruiting and activating APCs at the tumor site.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CAR-T therapy is used, then T cells can be engineered to express chimeric antigen receptors, but the therapy is ineffective in treating solid tumors due to insufficient activation of inflammatory response and inadequate recruitment of antigen-presenting cells
Solution Approach 1:
The patent combines CAR-T cells with APCs (antigen-presenting cells) into a dual-cell therapy approach. The CAR-T cells are co-administered with APCs that have been engineered to express specific antigens and co-stimulatory molecules, creating a synergistic system where APCs present tumor antigens to activate CAR-T cells more effectively at the tumor site, thereby resolving the insufficient inflammatory response activation problem
Solution Approach 2:
The patent introduces APCs as intermediary cells between the tumor antigens and CAR-T cells. These APCs serve as mediators that capture, process, and present tumor antigens to CAR-T cells, facilitating more effective immune activation. The APCs express co-stimulatory molecules that bridge the interaction between tumor cells and CAR-T cells, enhancing the inflammatory response at the tumor microenvironment
2Reliability
If conventional CAR-T therapy is used, then T cells can be engineered to express chimeric antigen receptors, but antigen-presenting cells are not sufficiently recruited or activated at the tumor site
Solution Approach 1:
The patent applies preliminary action by pre-engineering APCs before administration to express specific tumor antigens and co-stimulatory molecules. These APCs are prepared in advance with the necessary molecular equipment to recruit and activate CAR-T cells upon reaching the tumor site, ensuring that when the therapy is administered, the APCs are already equipped to perform their recruitment and activation functions effectively
Solution Approach 2:
The patent changes key parameters of APCs by engineering them to overexpress specific antigens and co-stimulatory molecules (such as CD80, CD86, CD40). This parameter modification transforms ordinary APCs into highly active immune recruiters that can effectively attract and activate CAR-T cells at the tumor microenvironment, increasing the quantity of activated APCs at the tumor site
Data Source
AI summary
Embodiments relate to compositions and methods for treating solid tumors. For example, the compositions comprise modified cells comprising an isolated polynucleotide comprising a polynucleotide encoding a nuclear factor of activated T cells (NFAT) promoter operatively associated with a polynucleotide encoding FLT3L.