Polyspecific Binding Molecules Enhance CAR T Cell Activation
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Solution Overview
Problem
Current immunotherapy for solid tumors, such as CAR T cell therapy, faces challenges due to the lack of timely activation of solid tumor CAR T cells, which prevents them from expanding and trafficking to tumor sites effectively.
Innovation Solution
The use of polyspecific binding molecules (PBMs) that bind both T cells and white blood cell antigens, enhancing the activation and expansion of modified cells, including CAR T cells, by contacting them with a population of cells comprising an antigen of a white blood cell and a PBM with a first binding domain for T cells and a second binding domain for the white blood cell antigen, allowing for increased expansion and activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR T cell therapy is used to treat solid tumors, then immunotherapy capability is provided, but timely activation and expansion of modified cells is insufficient
Solution Approach 1:
The patent introduces a polyspecific binding molecule (PBM) as an intermediary that bridges T cells and white blood cells. The PBM contains a first binding domain that binds to T cells and a second binding domain that binds to white blood cell antigens, facilitating timely activation and expansion of CAR T cells in the context of solid tumors where direct activation is insufficient.
2Ease of operation
If modified cells are contacted with white blood cell population without PBM, then basic immune interaction occurs, but expansion and activation levels are lower
Solution Approach 1:
The patent changes the binding parameters by introducing a PBM with specific binding domains. The PBM modifies the interaction parameters between T cells and white blood cells by providing controlled, high-affinity binding through engineered domains, thereby enhancing expansion and activation levels beyond natural immune interactions.
3Productivity
If PBM with first binding domain for T cell and second binding domain for white blood cell antigen is used, then activation and expansion of modified cells is enhanced, but treatment complexity increases
Solution Approach 1:
The PBM serves multiple functions simultaneously: it acts as a bridge between T cells and white blood cells, provides activation signals, and facilitates expansion of modified cells. This multi-functionality reduces the need for separate components or steps, thereby managing complexity while achieving enhanced productivity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach significantly enhances the activation and expansion of modified cells, improving their ability to target and treat solid tumors by increasing their presence at tumor sites and enhancing cytokine release, thereby improving treatment efficacy.
Implementation Method 1
a polyspecific binding molecule (PBM), the PBM comprising a first binding domain binding a T cell and a second binding domain binding the antigen of the WBC
Data Source
AI summary
The present disclosure relates to compositions and methods for enhancing cell response and/or expanding chimeric antigen receptor (CAR) cells and/or maintenance in vivo and/or in vitro. In embodiments, the method comprises obtaining CAR T cells comprising a CAR comprising a binding domain that binds a solid tumor antigen, a transmembrane domain, and an intracellular domain; and contacting the CART cells with white blood cells and a bispecific antibody, such as a Bispecific T cell engager (BiTE®), thereby activating the CAR T cells, wherein the level of activation of the CAR T cells is higher than the level of activation of CAR T ells that are contacted with B cells without the bispecific antibody. The bispecific antibody comprises a first binding domain binding CD3 and a second binding domain binding CD19, CD20, CD22, or BCMA.