Humanized Anti-CD94 Antibody for Low-Immunogenicity Checkpoint Therapy
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Solution Overview
Problem
Current immune checkpoint therapies targeting CD94 and NKG2A have limited research and treatment methods, and existing therapies like PD-1/L1 have low overall response rates, failing to benefit many patients and leading to tumor relapse and resistance.
Innovation Solution
Development of a murine anti-CD94 monoclonal antibody with a humanized constant region and retained CDRs, which exhibits high binding activity to human CD94 protein, effectively activating Jurkat T cells and potentially treating CD94-mediated diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If immune checkpoint therapy targets PD-1/L1, then treatment coverage is broadest, but overall response rate is only 30% and many patients experience tumor relapse and resistance
Solution Approach 1:
The patent segments the immune checkpoint therapy approach by targeting multiple distinct molecules (CD94, NKG2A, NKG2C) rather than relying on a single PD-1/L1 pathway. This segmentation allows different patients to be treated based on their specific tumor infiltrating lymphocyte phenotype, thereby improving response rates while maintaining broad coverage through multi-target therapy options.
2Ease of operation
If a single immune checkpoint therapy is used, then treatment protocol is simple, but it cannot be suitable for all patients due to heterogeneity in immune checkpoint receptor and ligand expressions
Solution Approach 1:
The patent introduces dynamic treatment selection based on patient-specific tumor infiltrating lymphocyte characteristics. The treatment protocol adapts to individual patient needs by determining which immune checkpoint molecules (CD94, NKG2A, NKG2C) are most relevant for each patient's tumor microenvironment, allowing the therapy strategy to evolve from static to dynamic based on real-time patient data.
3Measurement precision
If murine anti-CD94 monoclonal antibody is used, then binding activity to human CD94 is high, but immunogenicity in human patients increases
Solution Approach 1:
The patent uses humanized antibody constructs as an intermediary solution. These antibodies incorporate human constant regions and framework sequences while retaining the murine-derived CDRs responsible for CD94 binding. This intermediary approach maintains the high binding activity needed for therapeutic effectiveness while significantly reducing immunogenicity by minimizing foreign protein sequences in the human patient system.
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 humanized anti-CD94 antibody demonstrates low immunogenicity and specific binding to CD94, offering potential therapeutic benefits for diseases mediated by CD94, including cancer, autoimmune disorders, and transplant rejection.
Implementation Method 1
the humanized antibody can specifically target and bind to the human CD94 protein
Implementation Method 2
After binding to corresponding ligands, they transmit inhibitory signals into the immune cells, inhibiting an anti-cancer function of the immune cells
Data Source
AI summary
An anti-CD94 antibody and a use thereof. The antibody comprises heavy chain CDR1, CDR2, and CDR3, and light chain CDR1, CDR2, and CDR3, wherein: the amino acid sequences of the heavy chain CDR1, CDR2, and CDR3 respectively have at least 80% homology with the sequences represented by SEQ ID NOs 1, 2, and 3, and the amino acid sequences of the light chain CDR1, CDR2, and CDR3 respectively have at least 80% homology with the sequences represented by SEQ ID NOs 4, 5, and 6.