Chimeric Stimulating Molecules for Tumor Targeting
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Solution Overview
Problem
Conventional immunotherapy methods face deficiencies such as insufficient co-stimulatory signaling, inadequate specificity for cancer cells, and activation of immunosuppressive mechanisms, which limit their therapeutic effectiveness.
Innovation Solution
Development of modified immune cells, including tumor infiltrating lymphocytes (TILs) and T cells, equipped with chimeric stimulating molecules or switch molecules that fuse an extracellular domain eliciting an inactivation signal with an intracellular domain mediating activation, enhancing immune cell activation and specificity for tumor antigens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapy methods are used, then immune cells can recognize tumor antigens, but co-stimulatory signaling is insufficient leading to inadequate immune responses
Solution Approach 1:
The patent combines the extracellular domain of an immune checkpoint receptor (which normally transmits inactivation signals) with the intracellular domain of a co-stimulatory molecule (which transmits activation signals) to create a chimeric stimulating molecule. This merging allows the single molecule to both recognize tumor antigens and provide strong co-stimulatory signaling, resolving the contradiction between immune response effectiveness and signaling complexity
Solution Approach 2:
The chimeric stimulating molecule functions as a composite molecular structure that integrates functional domains from different immune receptors. The extracellular domain provides antigen recognition capability while the intracellular domain provides co-stimulatory signaling capability, creating a composite molecule that addresses the insufficiency of conventional single-function immune cell modifiers
2Productivity
If modified immune cells are created to enhance activation, then immune cell activation and proliferation increase, but specificity for cancer cells becomes inadequate leading to off-target effects
Solution Approach 1:
The chimeric stimulating molecule is designed with localized functional domains: the extracellular domain provides tumor antigen-specific recognition (specificity function) while the intracellular domain provides co-stimulatory signaling (activation function). This local differentiation of functions within the single molecule allows enhanced activation without compromising targeting specificity, as the antigen recognition function remains dedicated to specific tumor antigens
3Productivity
If immune cells are modified to increase cytotoxicity, then cancer cell elimination improves, but immunosuppressive mechanisms are activated reducing overall therapeutic effect
Solution Approach 1:
The patent converts the harmful immunosuppressive mechanism into a beneficial activation mechanism by taking an immune checkpoint receptor (which normally transmits inactivation signals when binding to its ligand) and reconfiguring it as a chimeric stimulating molecule. The extracellular domain of the checkpoint receptor is fused to the intracellular domain of a co-stimulatory molecule, so that instead of transmitting inhibition signals, the chimera transmits activation signals. This converts the原本是有害的免疫抑制机制 into a beneficial activation mechanism, resolving the contradiction between cancer cell elimination and immunosuppressive activation
Data Source
AI summary
Provided are modified immune cells including tumor infiltrating lymphocyte (TIL) or B cells, a composition comprising the immune cells, and a method of treating neoplastic or cancer conditions comprising administering to a subject the immune cells.