Anti-CD70 Antibody Humanization for Tumor Targeting
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current anti-CD70 antibody drugs are not effective for clinical application, and there is a need for novel anti-CD70 antibody drugs that can effectively target CD70, which is overexpressed in various tumors and promotes tumor growth by inducing regulatory T cells.
Innovation Solution
Development of a novel anti-CD70 antibody with specific heavy and light chain variable regions, including murine, chimeric, and humanized antibodies, with defined amino acid sequences and framework region mutations, which compete for binding to CD70 and inhibit CD70-induced CD27 signaling, thereby targeting and blocking CD70 expression on tumor cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-CD70 antibodies are used, then CD70 binding is achieved, but clinical effectiveness is insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure through humanization and affinity maturation. The variable regions were optimized with specific amino acid substitutions (e.g., in HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3) to enhance binding affinity to CD70, transforming the antibody from merely binding to effectively blocking CD70-mediated immune suppression and demonstrating potent antitumor activity in clinical settings.
Solution Approach 2:
The patent employs composite materials by creating a chimeric antibody structure that combines mouse variable regions (for antigen specificity) with human constant regions (for reduced immunogenicity and enhanced effector functions). This composite structure integrates the advantages of both murine and human antibody components, achieving both high affinity binding to CD70 and effective clinical application.
2Object-affected harmful factors
If CD70 induces regulatory T cells, then immune surveillance is evaded, but tumor growth is promoted
Solution Approach 1:
The patent applies preliminary anti-action by designing the anti-CD70 antibody to preemptively block the interaction between CD70 and its receptor before regulatory T cells can be induced. The antibody binds to CD70 with high affinity, preventing CD70 from engaging with its receptor and initiating the signaling pathway that would lead to regulatory T cell differentiation, thereby stopping immune surveillance evasion before it occurs.
Solution Approach 2:
The patent converts the harmful effect of CD70 into a beneficial therapeutic outcome by targeting and neutralizing CD70's immunosuppressive function. The anti-CD70 antibody transforms the pathological role of CD70 (promoting tumor growth through regulatory T cell induction) into a therapeutic opportunity, where blocking CD70 restores immune surveillance and generates antitumor immunity.
3Manufacturing precision
If anti-CD70 antibody drugs are developed, then CD70 targeting is achieved, but clinical application effectiveness remains insufficient
Solution Approach 1:
The patent applies preliminary action by conducting extensive in vitro and in vivo characterization studies before clinical application. The antibody underwent rigorous testing including binding affinity measurements, specificity assays against related antigens, effector function evaluations (ADCC, ADCP, CDC), and preclinical efficacy studies in tumor models, ensuring that the antibody demonstrated both high specificity and reliable therapeutic efficacy before advancing to clinical trials.
Solution Approach 2:
The patent employs feedback mechanisms through iterative optimization of the antibody structure based on performance data. Affinity maturation was achieved by selecting and combining variable region sequences that demonstrated superior binding characteristics in screening assays. The antibody design incorporated feedback from structural analysis, binding studies, and functional assays to refine the variable regions and maximize both specificity and therapeutic efficacy.
Data Source
AI summary
The present invention relates to an anti-CD70 antibody and an application thereof. Specifically, the present disclosure relates to an anti-CD70 antibody, which comprises a light chain variable region and a heavy chain variable region of the antibody, and a use as a drug.