Anti-PD-1 Antibody CDR Engineering for Stronger T Cell Activation
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Solution Overview
Problem
There is a need for the development of effective anticancer therapeutics targeting the PD-1 pathway to enhance T cell activation and cytokine secretion for improved cancer treatment.
Innovation Solution
Development of anti-PD-1 antibodies with specific CDR sequences, administered via intravenous, intramuscular, or subcutaneous routes, and comprising an Fc sequence of human IgG4, which enhance IL-2 and IFNγ secretion and T cell proliferation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-PD-1 treatments (e.g., OPDIVO) are used, then cancer treatment is provided, but efficacy in tumor growth inhibition and immune activation is insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure through specific CDR sequences (CDR-L1: KASQDVTTAVA, CDR-L2: WASTRHT, CDR-L3: QQHYTIPWT, CDR-H1: FTFSNYGMS, CDR-H2: TISGGGSNIY, CDR-H3: VSYYYGIDF) and using human IgG4 Fc sequence to enhance binding affinity and biological activity, thereby improving tumor growth inhibition and immune activation efficacy
Solution Approach 2:
The patent creates a composite therapeutic approach by combining the engineered anti-PD-1 antibody with specific administration routes (intravenous, intramuscular, or subcutaneous) and human IgG4 Fc sequence to achieve enhanced and sustained immune activation and tumor growth inhibition compared to existing treatments
2Reliability
If anti-PD-1 antibodies are administered to enhance T cell activation, then cytokine secretion is improved, but the complexity of antibody design increases
Solution Approach 1:
The patent applies segmentation by dividing the antibody into distinct functional regions with specifically engineered CDR sequences (L1, L2, L3, H1, H2, H3) and human IgG4 Fc sequence, allowing each segment to contribute specifically to binding affinity, specificity, and biological activity while maintaining overall antibody function
Solution Approach 2:
The patent achieves universality by designing an antibody that simultaneously performs multiple functions: blocking PD-1/PD-L1 interaction, enhancing T cell activation, promoting cytokine secretion (IL-2 and IFNγ), and stimulating T cell proliferation through the combination of engineered CDRs and human IgG4 Fc sequence
Data Source
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AI summary
Provided are anti-PD-1 antibodies, and antigen binding fragments thereof. Also provided are isolated nucleic acid molecules that encode the anti-PD-1 antibodies or antigen binding fragments thereof, related expression vectors, and host cells. Provided are methods of making anti-PD-1 antibodies, and antigen binding fragments thereof. Also provided are related pharmaceutical compositions and methods of their use to treat subjects.