Multispecific CD40-CD137 Antibodies for APC-T Cell Co-Activation
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Solution Overview
Problem
Existing therapies lack multispecific antibodies that can effectively bind both CD40 and CD137, failing to bring CD40-expressing antigen-presenting cells and CD137-expressing T cells into close contact for efficient activation and induction of anti-tumor immunity.
Innovation Solution
Development of multispecific antibodies with specific antigen-binding regions for CD40 and CD137, comprising unique CDR sequences and heavy chain constant regions, allowing simultaneous binding and activation of both cell types.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If monospecific antibodies against CD40 or CD137 are used separately, then each antibody can bind to its specific target, but the simultaneous activation of both APCs and T cells is limited
Solution Approach 1:
The patent combines two separate monospecific antibodies (anti-CD40 and anti-CD137) into a single multispecific antibody molecule that possesses both antigen-binding regions. This merging enables the antibody to simultaneously bind to CD40 on APCs and CD137 on T cells, achieving the desired versatility without requiring separate antibody administrations.
Solution Approach 2:
The multispecific antibody is designed to perform multiple functions: binding to CD40 on antigen-presenting cells, binding to CD137 on T cells, and thereby simultaneously activating both cell types. This multi-functionality resolves the contradiction by providing a single reagent that accomplishes what would otherwise require multiple separate agents.
2Productivity
If multispecific antibodies binding to both CD40 and CD137 are developed, then simultaneous activation of APCs and T cells is achieved, but manufacturing complexity increases
Solution Approach 1:
The multispecific antibody is constructed by segmenting the immune response function into distinct antigen-binding regions, each targeting a specific antigen (CD40 and CD137). This segmentation allows for modular design and facilitates the use of established monoclonal antibody technologies as building blocks, thereby managing manufacturing complexity while achieving enhanced productivity.
3Reliability
If existing monospecific antibodies are used, then binding specificity is maintained, but the ability to bring APCs and T cells into close contact is limited
Solution Approach 1:
By merging the binding specificities for CD40 and CD137 into a single multispecific antibody molecule, the invention maintains the reliability of specific binding while adding the operational advantage of simultaneously engaging both APCs and T cells. This enables the antibody to bring the two cell types into close contact, facilitating their interaction without compromising binding specificity.
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
The multispecific antibodies enhance T cell and APC activation, leading to robust CD8+ T-cell proliferation and ex vivo expansion of tumor-infiltrating lymphocytes, thereby bolstering the anti-tumor immune response.
Implementation Method 1
a multispecific antibody comprising (i) a first antigen-binding region binding to human CD40, and (ii) a second antigen-binding region binding to human CD137
Implementation Method 2
The multispecific antibodies induce intracellular signaling, mediate cell-to-cell interactions, and activate both CD40 and CD137
Data Source
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AI summary
Multispecific antibodies binding to human CD40 and human CD137, methods for preparing such multispecific antibodies, and methods of using such multispecific antibodies for therapeutic or other purposes.