Anti-CD47 Antibody CDR Engineering for Tumor Elimination
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Solution Overview
Problem
Current anti-CD47 antibodies often cause agglutination of red blood cells and have limited therapeutic efficacy in inhibiting tumor growth and macrophage phagocytosis, necessitating the development of antibodies with improved specificity and reduced side effects.
Innovation Solution
Development of a novel anti-CD47 antibody with specific binding capabilities to human CD47, comprising specific heavy and light chain complementary determining regions (CDRs) that inhibit CD47 binding to SIRPα, facilitating macrophage phagocytosis and tumor elimination without agglutination.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-CD47 antibodies are used to block CD47-SIRPα interaction and enhance macrophage phagocytosis, then tumor cell elimination is improved, but red blood cell agglutination occurs as a harmful side effect
Solution Approach 1:
The antibody is engineered with non-human primate CDRs specifically in the variable regions that bind to CD47, while the rest of the antibody structure remains humanized. This localized application of non-human sequences in the CDR regions provides high affinity and specificity for tumor cell CD47 without triggering red blood cell agglutination, resolving the contradiction between efficacy and side effects
Solution Approach 2:
The invention changes the amino acid sequence parameters of the CDR regions by using non-human primate sequences instead of fully human or chimeric sequences. This parameter change in the CDR region composition alters the binding characteristics to achieve selective binding to tumor CD47 while avoiding off-target binding to red blood cell CD47, thereby eliminating agglutination side effects
2Reliability
If existing anti-CD47 antibodies are used to inhibit tumor growth, then some therapeutic effect is achieved, but the efficacy is limited and complete tumor elimination is difficult
Solution Approach 1:
The antibody utilizes non-human primate CDR sequences which provide enhanced binding affinity and specificity for human CD47 on tumor cells. This parameter change in sequence composition results in more effective blocking of the CD47-SIRPα interaction, leading to enhanced macrophage phagocytosis and improved tumor elimination efficiency compared to conventional antibodies
3Reliability
If conventional anti-CD47 antibodies with broad binding are used, then CD47 binding is achieved, but specificity for tumor cells versus normal cells is reduced
Solution Approach 1:
The antibody employs non-human primate CDRs specifically in the antigen-binding regions to achieve high specificity for tumor cell CD47. This localized sequence optimization in the CDR regions enhances the ability to distinguish tumor cell CD47 from normal cell CD47, improving tumor cell specificity while maintaining binding capability
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 novel antibody effectively inhibits tumor growth and can lead to complete tumor disappearance with enhanced macrophage phagocytosis and reduced side effects by specifically targeting CD47, overcoming the limitations of existing antibodies.
Implementation Method 1
The present invention is directed to a novel antibody which binds specifically to the integrin-associated protein (IAP), (also named CD47)
Data Source
AI summary
The present invention is directed to a novel antibody against CD47 and the antibody fragments thereof and a composition comprising the antibody or antibody fragments thereof. The present invention relates further to a nucleic acid encoding the antibodies or antibody fragments thereof and host cells comprise the same, as well as the relevant use of the same. In addition, the present invention is also directed to the use of these antibodies and antibody fragments in the therapy and diagnosis.