PD-L1 Binding Peptides for Cancer Immunotherapy
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Solution Overview
Problem
Current cancer immunotherapy using PD-1/PD-L1 blockade has limitations due to high production costs, immunogenicity, and incomplete understanding of immune modulation, with many patients not responding to therapy.
Innovation Solution
Development of peptides specifically binding to PD-L1, such as PD-L1Pep-1 and PD-L1Pep-2, which inhibit PD-L1 function, activating immune cells against cancer cells, and are used in compositions for diagnosis, treatment, and drug delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If selective monoclonal antibodies targeting PD-L1 are used for cancer immunotherapy, then antitumor response and clinical benefit are improved, but production cost increases and immunogenicity occurs
Solution Approach 1:
The patent creates simplified peptide copies of the full PD-L1 blocking antibody structure. These peptides (e.g., sequences like Cys-Leu-Gln-Lys-Thr-Pro-Lys-Gln-Cys) replicate the essential PD-L1 binding function while being much simpler to produce through chemical synthesis rather than complex antibody manufacturing processes, thereby reducing production costs while maintaining therapeutic efficacy
Solution Approach 2:
The patent employs small peptides as disposable, easily replaceable therapeutic agents. These short peptide sequences can be synthesized cheaply and replaced if needed, unlike expensive monoclonal antibodies. The peptides serve their PD-L1 blocking function and can be administered as needed without the high manufacturing burden of full antibody production
2Reliability
If selective monoclonal antibodies targeting PD-L1 are used for cancer immunotherapy, then antitumor response is improved, but immunogenicity increases
Solution Approach 1:
The patent uses simplified peptide copies instead of full-length antibodies. These minimal peptide sequences (7-20 amino acids) that specifically bind PD-L1 are less likely to be recognized as foreign by the patient's immune system compared to large protein antibodies, thereby reducing immunogenicity while preserving the essential PD-L1 blocking function needed for antitumor response
Solution Approach 2:
The patent extracts only the critical PD-L1 binding domain from the full antibody structure. By isolating and using just the essential peptide sequence that binds PD-L1 (removing the rest of the antibody protein), the invention reduces the foreign protein content that would trigger immune responses, thereby lowering immunogenicity while maintaining therapeutic effect
3Reliability
If PD-1 blockade therapy is administered to cancer patients, then clinical response is achieved in some patients, but many patients fail to respond and the mechanism is not fully understood
Solution Approach 1:
The patent focuses on the specific local interaction between PD-L1 and its binding partner. By designing peptides that target the precise PD-L1 binding site with high specificity, the invention enhances the local blocking effect at the PD-1/PD-L1 interface. This localized, high-affinity binding may improve clinical response rates by more effectively preventing the immunosuppressive interaction in the tumor microenvironment
Solution Approach 2:
The patent optimizes parameters such as peptide sequence, length, and binding affinity to enhance PD-L1 blockade efficacy. By systematically varying and optimizing these parameters (e.g., testing different peptide sequences like the 9-amino acid vs. 7-amino acid variants), the invention seeks to identify the most effective configurations for blocking PD-L1, potentially improving clinical response rates and providing insights into the mechanism of action
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 peptides demonstrate strong anticancer effects by enhancing CD8+ T cell proliferation and cytokine production, similar to antibodies, with potential for stable blood circulation and reduced side effects, offering a promising immunotherapy approach.
Implementation Method 1
a peptide specifically bound to PD-L1 comprising the amino acid sequence represented by SEQ ID NO: 1 or SEQ ID NO: 2
Implementation Method 2
inhibits it, thereby activating the function of immune cells against cancer cells and exhibiting anticancer effects
Data Source
AI summary
The present invention relates to a peptide bound to PD-L1 and uses for cancer immunotherapy and anticancer using the same, and the peptide of the present invention specifically binds to PD-L1 and inhibits it, thereby activating the function of immune cells against cancer cells and exhibiting anticancer effects. The peptides of the present invention selected two peptides (PD-L1Pep-1 and PD-L1Pep-2) that bind well to cells with high expression of human PD-L1 protein using phage peptide display technology and it was confirmed that it inhibits its function by binding to PD-L1 in humans and mice. The peptide of the present invention showed an effect similar level to that of an antibody and is relatively stable in blood, indicating a high potential as a cancer immunotherapy in the future.