PD-L1 Binding Proteins for Solid Tumor Treatment
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Solution Overview
Problem
Current Adoptive Cell Transfer (ACT) therapies face challenges in overcoming the inhibitory effect of the PD-1-PD-L1 interaction, which limits the anti-tumor immune response in cancer treatment.
Innovation Solution
Development of proteins, such as antibodies and genetically modified cytotoxic lymphocytes, that specifically bind to PD-L1 to reduce the interaction between PD-L1 and PD-1, allowing for enhanced anti-tumor activity by secreting PD-L1 binding proteins like scFV or maxibodies to 'relieve' the inhibitory effect of the PD-1 checkpoint.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ACT therapy uses TILs to treat cancer, then anti-tumor immune response is enhanced, but the PD-1-PD-L1 interaction limits the anti-tumor activity
Solution Approach 1:
The patent introduces an anti-PD-L1 antibody as an intermediary substance that binds to PD-L1 on tumor cells, preventing the PD-1 receptor on TILs from interacting with PD-L1. This mediator blocks the inhibitory signal transmission from tumor cells to T-cells, thereby maintaining the anti-tumor activity of TILs while treating the harmful inhibitory effect.
2Reliability
If genetically modified cytotoxic lymphocytes secrete PD-L1 binding proteins, then the inhibitory effect of PD-1 checkpoint is relieved, but the complexity of cell manipulation increases
Solution Approach 1:
The patent genetically modifies cytotoxic lymphocytes to autonomously secrete PD-L1 binding proteins (such as scFv or maxibodies). The modified cells self-service by producing their own protective mechanism against PD-1-mediated inhibition, eliminating the need for external administration of antibodies and simplifying the overall treatment protocol despite the initial genetic modification complexity.
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 approach enables improved anti-cancer effects by enhancing the anti-tumor response of genetically modified TILs, allowing them to effectively target and eliminate tumor cells by blocking the PD-1/PD-L1 interaction, thereby improving treatment outcomes for solid tumors.
Implementation Method 1
proteins, such as antibodies, that include an antigen binding portion that specifically binds to Programmed Death 1 Ligand 1 (PD-L1)
Data Source
Figure 1
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Figure 3A~3B
AI summary
The present disclosure provides proteins, such as antibodies, that include an antigen binding portion that specifically binds to Programmed Death 1 Ligand 1 (PD-L1). Also provided are nucleic acids encoding the proteins, and cells (e.g., genetically modified cytotoxic lymphocytes) that include such nucleic acids. In some embodiments, a subject method includes reducing the interaction between PD-L1 on a first-cell and PD-1 on a second cell. In some cases, the contacting is in vivo. For example, the methods and compositions provided can be used in the treatment of viral infection and cancer, such as the treatment of solid tumors via ACT or via administration of a subject protein that specifically binds to PD-L1.