Anti-PDL1 Aptamers Block Tumor Immune Evasion
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Solution Overview
Problem
The overexpression of PDL1 on cancer cells leads to tumor immune evasion by impairing T cell function, resulting in poor cancer treatment outcomes, highlighting the need for therapeutic agents that can interfere with the PD-1:PDL1 interaction.
Innovation Solution
Development of anti-PDL1 nucleic acid aptamers that bind to PDL1, preventing the PD-1:PDL1 interaction and neutralizing its inhibitory activity, thereby enhancing immune activity and suppressing tumor growth.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If PDL1 is overexpressed on cancer cells to enhance immune evasion, then tumor immune evasion capability is improved, but cancer treatment outcomes deteriorate
Solution Approach 1:
The patent introduces aptamers as intermediary molecules that bind to PDL1 on cancer cells, preventing the direct interaction between PDL1 and PD-1 on T cells. This intermediary binding blocks the immune evasion pathway while preserving T cell anti-tumor activity, thereby resolving the contradiction between maintaining immune evasion capability and improving treatment outcomes
Solution Approach 2:
The patent changes the binding parameters of PDL1 by introducing aptamers with high affinity and specificity. These aptamers alter the equilibrium of PDL1 interactions, shifting it from PD-1 binding to aptamer binding, thus reducing the harmful immune suppression while maintaining PDL1's natural function at controlled levels
2Reliability
If monoclonal antibodies are used to block PD-1:PDL1 interaction, then immune activity is enhanced, but molecular weight and tissue penetration capability worsen
Solution Approach 1:
The patent uses aptamers as simplified copies or alternatives to monoclonal antibodies. Instead of using large protein-based antibodies, the invention employs smaller nucleic acid-based aptamers that replicate the blocking function of antibodies by binding to PDL1, thus achieving similar immune enhancement with reduced molecular weight and improved tissue penetration
Solution Approach 2:
The patent employs aptamers that can be chemically synthesized at lower cost and with easier modification compared to monoclonal antibodies. These aptamers, while potentially having shorter half-lives, can be rapidly produced and optimized, providing a cost-effective alternative that achieves the desired therapeutic effect without the complexity and high cost of antibody production
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 anti-PDL1 aptamers effectively block the PD-1:PDL1 interaction, leading to significant tumor suppression in vivo and enhanced immune activity, offering a promising therapeutic approach for cancer treatment and infectious diseases.
Implementation Method 1
Aptamers are short nucleic acid (DNA or RNA) molecules that are capable of forming secondary structures or even complex three-dimensional structures and have specific binding activities to target proteins
Data Source
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AI summary
Aptamers that bind to and antagonize PDL1 and uses thereof in enhancing immune activity (e.g., promoting T cell proliferation), treating cancer, and/or infectious diseases such as infections caused by enterovirus, HBV, or HCV infection.