CAR-T Therapy With Antigen-Expressing Cells for Immune Memory
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Solution Overview
Problem
Current CAR-T cell therapies for cancer, particularly in relapsed/refractory B-ALL, face challenges in sustaining remission due to poor persistence of CAR-T cells, leading to tumor recurrence, and repeated administrations induce immune clearance, lacking strategies to induce immune memory.
Innovation Solution
Administer therapeutic T cells targeting cancer-related antigens in conjunction with cells expressing those antigens to stimulate immune memory and prolong persistence in vivo.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR-T cells are administered to treat cancer, then tumor elimination efficacy is improved, but CAR-T cell persistence in vivo deteriorates leading to tumor recurrence
Solution Approach 1:
The patent applies preliminary action by administering antigen-expressing cells (such as dendritic cells or tumor cells) before or concurrently with CAR-T cells to pre-condition the immune system. This preliminary exposure to antigens enhances the persistence and efficacy of subsequently administered CAR-T cells, addressing the problem of poor CAR-T cell persistence through advance immune system preparation
Solution Approach 2:
The patent uses antigen-expressing cells as intermediaries between the CAR-T cells and the tumor antigens. These intermediary cells present tumor-associated antigens to the CAR-T cells in a controlled manner, enhancing CAR-T cell activation, persistence, and anti-tumor efficacy while reducing direct CAR-T cell exhaustion from continuous tumor antigen exposure
2Reliability
If repeated administrations of CAR-T cells are performed, then tumor elimination is improved, but immune clearance against engineered T cells increases
Solution Approach 1:
The patent extracts the antigen presentation function from the tumor cells themselves and transfers it to separate antigen-expressing cells (such as dendritic cells or engineered tumor cells). This separation allows the immune system to be trained on antigens without the harmful effects of repeated high-dose CAR-T cell administrations, reducing immune clearance while maintaining tumor elimination efficacy
Solution Approach 2:
The patent applies preliminary action by using antigen-expressing cells to prime the immune response before CAR-T cell administration. This preliminary antigen exposure creates immunological memory that reduces the need for repeated CAR-T cell administrations, thereby decreasing immune clearance against engineered T cells while maintaining effective tumor elimination
3Reliability
If CAR-T cell therapy is administered, then remission is achieved, but strategies to induce immune memory are lacking leading to sustained remission failure
Solution Approach 1:
The patent uses antigen-expressing cells as intermediaries to bridge the gap between CAR-T cell therapy and immune memory induction. These intermediary cells continuously present tumor antigens to CAR-T cells in a controlled manner, promoting the differentiation of CAR-T cells into memory phenotypes and establishing long-term immunological surveillance that sustains remission
Solution Approach 2:
The patent applies periodic action through the continuous but controlled presentation of tumor antigens by antigen-expressing cells. This periodic antigen stimulation maintains CAR-T cell persistence and promotes memory cell formation without causing excessive immune activation or exhaustion, thereby achieving sustained remission
Data Source
AI summary
The present invention belongs to the field of biomedicine. Specifically, the present invention relates to an improved T-cell therapy. More specifically, the present invention relates to enhancing the cancer treatment efficacy of therapeutic T cells (such as CAR-T or TCR-T cells) through stimulation with living cells expressing cancer-related antigens.