Humanized IgG1 CD3 Antibodies for Lower Immunogenicity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing CD3 antibodies, such as catumaxomab and ertumaxomab, suffer from immunogenicity and severe adverse effects like cytokine storms, limiting their clinical efficacy and long-term use in humans, while cross-reactive antibodies for non-human CD3 have not been fully optimized.
Innovation Solution
Development of humanized or chimeric IgG1 antibodies with specific VH and VL regions, capable of binding to human CD3 and potentially other primate CD3, with optimized sequences to minimize immunogenicity and enhance efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mouse/rat hybrid antibodies (catumaxomab) are used for cancer treatment, then cytotoxic efficacy against tumor cells is achieved, but immunogenicity increases and severe adverse effects (cytokine storms) occur
Solution Approach 1:
The patent applies parameter changes by humanizing the antibody sequence - specifically changing the species origin parameter from mouse/rat hybrid to humanized/chimeric IgG1 format. This fundamental parameter change maintains the cytotoxic efficacy against tumor cells while reducing immunogenicity and adverse effects like cytokine storms, enabling long-term intravenous treatment in humans.
Solution Approach 2:
The patent uses composite materials by creating a chimeric antibody structure that combines different species components - human IgG1 constant regions with variable regions derived from non-human sources. This composite structure allows the antibody to maintain high affinity binding to CD3 while being more compatible with the human immune system, reducing rejection and adverse reactions.
2Adaptability or versatility
If cross-reactive antibodies for non-human CD3 are developed, then binding capability to primate CD3 is achieved, but specificity and reduced immunogenicity are not fully optimized
Solution Approach 1:
The patent applies local quality by making targeted amino acid substitutions in specific regions of the antibody - particularly in the variable regions that contact the antigen. These localized changes optimize binding to human CD3 while maintaining or reducing cross-reactivity to primate CD3, achieving high specificity with reduced immunogenicity in the regions most critical for antigen recognition.
Data Source
Figure 1A~1B
Figure 2A~2B
Figure 3A~3B
AI summary
The present invention relates to humanized or chimeric antibodies binding CD3. It furthermore relates to bispecific antibodies, compositions, pharmaceutical compositions, use of said antibodies in the treatment of a disease, and method of treatment.