Multispecific Molecules Targeting TAMs and MDSCs
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Solution Overview
Problem
Current therapies fail to effectively target and deplete tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), which are immunosuppressive cells that contribute to tumor growth and immune evasion.
Innovation Solution
Development of novel multispecific molecules comprising two different immunosuppressive myeloid cell binding moieties, such as antibody molecules, that specifically target TAMs or MDSCs, including binding to antigens like CSF1R, CCR2, and PD-L1, to deplete these cells while sparing other immune cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used to target TAMs and MDSCs, then treatment is simpler and fewer targets are involved, but the therapies fail to effectively deplete these immunosuppressive cells
Solution Approach 1:
The patent combines two different binding moieties into a single multispecific molecule, where the first moiety binds to one target antigen on TAMs/MDSCs and the second moiety binds to a different target antigen. This merging approach enhances depletion effectiveness by simultaneously engaging multiple targets while maintaining a single therapeutic agent structure.
Solution Approach 2:
The multisspecific molecule is designed with multiple binding moieties that can recognize different antigens expressed on immunosuppressive cells, enabling a single therapeutic to perform multiple targeting functions. This multi-functionality allows the molecule to effectively deplete TAMs and MDSCs through various binding interactions rather than relying on a single target.
2Reliability
If broad targeting is used to deplete myeloid cells, then more immunosuppressive cells are depleted, but homeostatic myeloid cells are also adversely affected
Solution Approach 1:
The binding moieties in the multispecific molecule are designed to recognize specific antigens that are locally expressed on the surface of immunosuppressive cells like TAMs and MDSCs, rather than targeting universal markers. This localized targeting approach ensures that only cells expressing these specific antigens are depleted, sparing homeostatic myeloid cells that do not express them.
Solution Approach 2:
The patent uses specific antigens as intermediaries to distinguish between immunosuppressive cells and homeostatic cells. By targeting antigens that are selectively expressed on TAMs and MDSCs but not on homeostatic myeloid cells, the therapeutic achieves selective depletion without adversely affecting normal cell populations.
Data Source
AI summary
Multispecific molecules targeting tumor associated macrophages (TAMs) or myeloid derived suppressor cells (MDSCs) and methods of using the same, are disclosed.