Humanized Anti-GPC3 Antibodies for CAR-T Specificity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current immunotherapy methods for tumors, particularly those using CAR T cells, face challenges in finding suitable antigen genes due to the complexity of gene expressions and uncontrollable factors, and there is a lack of effective anti-Glypican-3 (GPC3) antibodies for targeting hepatocellular carcinoma and other tumors.
Innovation Solution
Development of specific antibodies, such as P7D4 and am4, which recognize GPC3 with enhanced affinity, and their use in creating chimeric antigen receptors (CARs) for immune cells to target tumor cells expressing GPC3, along with the production of immunoconjugates and genetically modified immune cells for tumor treatment and diagnosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If adoptive immunotherapy based on immune effector cells is used, then therapeutic effects can be achieved in some tumors, but the therapeutic effects in most tumors are still unsatisfactory
Solution Approach 1:
The patent changes the key parameter of antigen target selection by identifying GPC3 as a novel tumor-specific antigen that is highly expressed in hepatocellular carcinoma but absent in normal adult liver tissue. This parameter change enables CAR T cells to effectively target hepatocellular carcinoma while avoiding off-target effects on normal liver tissue, thereby improving both therapeutic effect and tumor-specific adaptability
2Reliability
If T cell receptors (TCRs) are used for antigen recognition, then CAR T lymphocytes can selectively target tumor cells, but it is very difficult to find suitable antigen genes due to the complexity of gene expressions
Solution Approach 1:
The patent extracts and isolates GPC3 as a specific antigen target from the complex landscape of tumor-associated antigens. By focusing on GPC3's unique expression pattern (highly expressed in hepatocellular carcinoma, absent in normal adult liver), the patent simplifies the antigen selection process and provides a clear, actionable target for CAR T cell therapy against hepatocellular carcinoma
3Reliability
If mouse anti-mesothelin antibodies are used for CAR T cell construction, then tumor targeting can be achieved, but allergic reactions occur that affect long-term survival in human body
Solution Approach 1:
The patent changes the immunogenicity parameter by selecting GPC3 as the target antigen, which is human-derived and highly specific to hepatocellular carcinoma. This parameter change eliminates the need for mouse antibodies, thereby avoiding allergic reactions while maintaining effective tumor targeting capability through humanized CAR T cell construction
Data Source
AI summary
The present invention provides an antibody against glypican-3 (GPC3) and application thereof, and the antibody comprises a single chain antibody and humanized antibody.