Immunomodulator Compounds for PD-L1 Surface Internalization
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Solution Overview
Problem
Cancer cells evade immune system suppression by upregulating PD-L1, leading to inhibitory signaling that reduces immune response, necessitating new compounds to block PD-1/PD-L1 interaction.
Innovation Solution
Development of compounds that induce PD-L1 internalization from the cell surface, reducing PD-L1 availability for ligand engagement and inhibitory signaling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If cancer cells upregulate PD-L1 expression on cell surface, then immune evasion is enhanced, but inhibitory signaling to immune response increases
Solution Approach 1:
The patent extracts PD-L1 from the cell surface through internalization mechanisms. Compounds or antibodies induce PD-L1 to be internalized into the cell, removing it from the extracellular environment where it would otherwise bind PD-1 and deliver inhibitory signals. This extraction directly addresses the harmful inhibitory signaling while preserving the cell's ability to express PD-L1 when needed.
Solution Approach 2:
The patent introduces intermediary compounds or antibodies that mediate the interaction between PD-L1 and PD-1. These intermediaries bind to PD-L1 on the cell surface and trigger its internalization, effectively blocking the PD-1/PD-L1 interaction pathway without permanently eliminating PD-L1 expression capability.
2Object-generated harmful factors
If PD-L1 is blocked from binding PD-1, then inhibitory signaling is reduced, but PD-L1 availability for ligand engagement decreases
Solution Approach 1:
The patent introduces dynamic control over PD-L1 availability through regulated internalization. Rather than permanently reducing PD-L1 expression, the system dynamically shifts PD-L1 between surface-bound (available for engagement) and internalized (removed from signaling pathway) states based on therapeutic intervention, allowing flexible control of both engagement capability and inhibitory signaling.
Solution Approach 2:
The patent changes the spatial and functional parameters of PD-L1 through internalization. By altering the location of PD-L1 from the cell surface to the intracellular space, the system modifies its availability for ligand engagement while simultaneously removing it from the extracellular signaling environment, thus decoupling the two functions.
3Reliability
If PD-L1 internalization is induced, then immune response is enhanced, but compound complexity increases
Solution Approach 1:
The patent develops compounds or antibody formats that perform multiple functions: binding to PD-L1, inducing internalization, and blocking PD-1/PD-L1 interaction. This multi-functionality is achieved through carefully designed molecular structures that can simultaneously engage PD-L1 and trigger its internalization pathway, reducing the need for separate therapeutic agents.
Solution Approach 2:
The patent optimizes compound parameters such as binding affinity, internalization efficiency, and pharmacokinetic properties to achieve effective immune response enhancement. By tuning these parameters, the system achieves therapeutic efficacy while managing compound complexity through rational drug design and selection of promising candidates.
Data Source
AI summary
Compositions and methods for inducing PD-L1 internalization are disclosed. The methods include reducing the amount of cell surface PD-L1 by contacting a cell expressing PD-L1 with a compound that binds to cell surface PD-L1 and induces PD-L1 internalization. Compounds that induce PD-L1 internalization can be used to enhance, stimulate and/or increase an immune response and treat a PD-1-related disease or condition.