Neutralizing Antibody Against GDF15 for Treatment of Cancer-associated Cachexia

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2024 Aug 22

PMID 39172988

Authors

Junyi Xiong

Guojin Wu

Jinying Ning

Junlin Yan

Jian Yang

Jinsen Kang

Affiliations

Soon will be listed here.

Abstract

GDF15 (growth differentiation factor 15), also known as macrophage inhibitory cytokine 1 (MIC-1), is a circulating protein involved in the regulation of energy balance and weight control. Elevated levels of GDF15 have been associated with cachexia and reduced survival rates in cancer patients. Through the activation of the GFRAL (GDNF-family receptor α-like)-RET (Rearranged during Transfection) signaling pathway, GDF15 can induce weight loss, making it a potential target for treating cachexia. Currently, there are no approved antibody drugs specifically targeting GDF15 for cancer cachexia treatment. However, efforts have been made to develop antibody-based therapeutics against this emerging target. In this study, we generated a monoclonal antibody KY-NAb-GDF15 against GDF15 that effectively blocks downstream signaling mediated by GFRAL upon stimulation by GDF15. This antibody demonstrates robust neutralizing activity and exhibits high binding specificity. Importantly, our findings indicate that this antibody holds promise in alleviating cancer-induced cachexia and mitigating chemotherapy-induced weight loss, thereby offering significant therapeutic potential for managing cancer cachexia.

Citing Articles

Characterization of a Cancer-Induced Bone Pain Model for Use as a Model of Cancer Cachexia.

Hasegawa T, Kawahara K, Sato K, Asano Y, Maeda T Curr Issues Mol Biol. 2024; 46(12):13364-13382.

PMID: 39727925 PMC: 11726747. DOI: 10.3390/cimb46120797.

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