Humanized Anti-PD-L1 Antibody Reducing Immunogenicity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current PD-L1 monoclonal antibodies for cancer treatment have limitations, including induction of immunogenicity and excessive checkpoint signaling that can lead to autoimmune diseases, necessitating the development of new antibodies that can effectively block the PD-1/PD-L1 interaction with fewer side effects.
Innovation Solution
A humanized anti-human PD-L1 monoclonal antibody with specific amino acid sequences in its heavy and light chain variable regions, designed to have high affinity and specificity for PD-L1, indirectly blocking the PD-1/PD-L1 interaction and activating T cells to secrete cytokines, thereby relieving immunosuppression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing PD-L1 monoclonal antibodies are used for cancer treatment, then tumor immunotherapy effect is achieved, but immunogenicity is induced and excessive checkpoint signaling occurs leading to autoimmune diseases
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequences in the variable regions of the antibody (heavy chain variable region sequences SEQ ID NO:9-16 and light chain variable region sequences SEQ ID NO:17-24) to create a humanized antibody with altered binding characteristics. This changes the molecular parameters of the antibody to reduce immunogenicity while maintaining therapeutic efficacy against PD-L1
Solution Approach 2:
The patent uses copying by creating a humanized version of the anti-PD-L1 antibody. The humanized antibody copies the functional structure of existing anti-PD-L1 antibodies but uses human amino acid sequences in the variable regions, thereby copying the therapeutic function while reducing the harmful immunogenicity associated with non-human antibodies
2Reliability
If PD-L1 monoclonal antibodies block the PD-1/PD-L1 interaction, then T cell activation is enhanced, but excessive checkpoint signaling occurs
Solution Approach 1:
The patent applies partial action by designing the humanized antibody to provide just enough blocking activity to achieve T cell activation without excessive signaling. The specific amino acid sequences in the variable regions are optimized to create moderate-affinity binding that activates T cells sufficiently for tumor treatment while avoiding over-activation that would cause autoimmune effects
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 antibody effectively enhances the immune response against tumors by specifically binding to PD-L1, reducing immunosuppression and promoting cytokine secretion, offering a new mechanism for immune checkpoint regulation with potentially fewer side effects compared to existing antibodies.
Implementation Method 1
A humanized anti-human PD-L1 monoclonal antibody with specific amino acid sequences in its heavy and light chain variable regions, designed to have high affinity and specificity for PD-L1, indirectly blocking the PD-1/PD-L1 interaction
Data Source
AI summary
The present invention relates to a humanized anti-human PD-L1 monoclonal antibody, and a preparation method and use thereof. The humanized anti-human PD-L1 monoclonal antibody provided in the present invention has high affinity and specificity for PD-L1, stimulates T cells to secrete cytokines, and specifically relieves the negative immune regulation by PD-L1. The effect of this antibody is not achieved by directly blocking the interaction between PD-1 and PD-L1, presenting a new mechanism of immune checkpoint regulation. Therefore, the functional humanized anti-human PD-L1 monoclonal antibody provided in the present invention activates T cells by regulating the PD-L1 signaling pathway, thereby achieving the purpose of tumor immunotherapy.