Anti-GFRAL Antibody CDR Sequence Optimization for Cachexia Treatment
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for cancer-related anorexia-cachexia syndrome (CACS) and side effects of chemotherapy are inadequate, with a lack of effective options for managing weight loss, muscle breakdown, and appetite suppression, particularly due to the involvement of GDF15 and its receptor GFRAL.
Innovation Solution
Development of an anti-GFRAL antibody with improved affinity, including specific heavy and light chain CDR sequences, to enhance binding ability and inhibit GFRAL signaling, thereby mitigating cachexia and chemotherapy-induced side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-GFRAL antibodies are used, then GFRAL binding is achieved, but binding affinity is insufficient to effectively mitigate cachexia
Solution Approach 1:
The patent applies parameter changes by modifying the CDR sequences of the antibody to optimize binding affinity. Specifically, the heavy chain CDR1 sequence was changed from GFTFSSYGIS to GFTFSSYGID, and CDR3 from YDGK to YDGY, while the light chain CDR2 was modified from WSGN to WSGD. These sequence parameter changes result in improved binding affinity to GFRAL and enhanced therapeutic efficacy in mitigating cancer cachexia.
2Adaptability or versatility
If general appetite stimulants and muscle synthesis stimulants are used, then treatment options are provided, but they fail to effectively treat cancer-related anorexia-cachexia syndrome
Solution Approach 1:
The patent uses GFRAL antibody as an intermediary to block the GDF15-GFRAL signaling pathway. Instead of directly stimulating appetite or muscle synthesis, the antibody mediates the inhibition of the underlying pathological mechanism by binding to GFRAL and preventing GDF15 from activating it, thereby effectively treating cancer cachexia where conventional stimulants fail.
3Quantity of substance
If GDF15 concentration increases in cancer patients, then cachexia is induced through anorexia, but effective treatment options are lacking
Solution Approach 1:
The patent applies preliminary anti-action by administering the anti-GFRAL antibody before the full development of cachexia symptoms. The antibody preemptively blocks the GFRAL receptor, preventing GDF15 from exerting its harmful effects even when GDF15 concentration is elevated, thereby preventing weight loss and muscle breakdown before they occur.
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 anti-GFRAL antibody with improved affinity effectively increases weight, reduces muscle and fat loss, and enhances appetite, demonstrating significant mitigation of cancer cachexia and chemotherapy side effects in mouse models.
Implementation Method 1
anti-GFRAL antibody with improved affinity... enhance binding ability and inhibit GFRAL signaling
Data Source
AI summary
The present invention relates to a GFRAL-antagonistic antibody having improved affinity and a use thereof, and more particularly, the present invention relates to an anti-GFRAL antibody having improved affinity, comprising a heavy chain CDR and a light chain CDR of specific sequences, or an antigen-binding fragment thereof. The anti-GFRAL antibody having improved affinity exhibits higher binding ability to a GFRAL protein than a conventional anti-GFRAL antibody, and thus is expected to be effectively used for improving or treating cancer-related anorexia or cachexia syndrome and side effects of chemotherapy anticancer drugs.