Antigen-Presenting Cells Enhance CAR T Cell Expansion and Activation
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Solution Overview
Problem
Current immunotherapy methods, such as CAR T cell therapy, are limited in effectively treating solid tumors and require enhancement to improve their efficacy and expandability for cancer treatment.
Innovation Solution
A method involving the administration of cells expressing antigen binding molecules and antigen-presenting cells to stimulate lymphocytes, specifically T cells and NK cells, to activate and expand them, using dendritic cells, macrophages, and other APCs to enhance immune response against solid tumor antigens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR T cell therapy is used to treat solid tumors, then immune response is activated, but treatment efficacy is insufficient
Solution Approach 1:
The patent introduces antigen-presenting cells (APCs) as intermediary cells that bridge the gap between CAR T cells and solid tumor antigens. The APCs process and present tumor-associated antigens to CAR T cells, enabling effective recognition and activation even when tumors do not directly express high levels of target antigens. This mediator approach resolves the contradiction by providing an indirect pathway for immune recognition.
Solution Approach 2:
The patent employs in vitro pre-activation and expansion of CAR T cells using APCs before clinical administration. This preliminary action enhances the potency and functionality of CAR T cells ex vivo, ensuring they are fully activated and expanded to therapeutic levels before being infused into patients, thereby improving treatment efficacy against solid tumors.
2Quantity of substance
If lymphocytes are expanded in vitro, then cell numbers increase, but activation and functionality may be compromised
Solution Approach 1:
APCs serve as intermediary cells during in vitro expansion, providing continuous antigen presentation and co-stimulatory signals to lymphocytes. This ensures that expansion occurs in the presence of physiological activation signals, maintaining cell functionality and preventing exhaustion that would occur with conventional cytokine-only expansion methods.
Solution Approach 2:
The patent implements continuous co-culture of lymphocytes with APCs throughout the expansion process, ensuring uninterrupted antigen presentation and immune stimulation. This continuous useful action maintains lymphocyte activation states and functional capabilities throughout the expansion period, preventing loss of functionality that occurs with discontinuous or cytokine-only methods.
3Reliability
If multiple cell types are used for immunotherapy, then immune response is enhanced, but treatment complexity increases
Solution Approach 1:
The patent employs APCs that perform multiple functions: they present antigens to activate CAR T cells, provide co-stimulatory signals for expansion, and secrete cytokines to enhance immune response. This multi-functionality consolidates several therapeutic actions into a single cell type, reducing overall treatment complexity while maintaining enhanced immune response.
Solution Approach 2:
The patent combines antigen presentation, co-stimulation, and cytokine production functions into the APC component, merging multiple immune-enhancing mechanisms into a unified therapeutic approach. This consolidation simplifies the treatment protocol by using a single dual-function cell population rather than requiring separate administrations of different cell types or factors.
Data Source
AI summary
The present disclosure relates to compositions and methods for enhancing T cell response and/or CAR cell expansion and/or maintenance in vivo and/or in vitro. For example, in a method of in vivo cell expansion, the method comprises administering an effective amount of cells comprising an antigen binding molecule to a subject; and administering an effective amount of presenting cells expressing a solid tumor antigen that the binding molecule binds.