{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:21:56Z","timestamp":1784762516896,"version":"3.55.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research and Development Program of Xinjiang","award":["2022B02055-3"],"award-info":[{"award-number":["2022B02055-3"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>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 \u03b1-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.<\/jats:p>","DOI":"10.1371\/journal.pone.0309394","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T19:11:58Z","timestamp":1724353918000},"page":"e0309394","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Neutralizing antibody against GDF15 for treatment of cancer-associated cachexia"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8181-3436","authenticated-orcid":true,"given":"Junyi","family":"Xiong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinying","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsen","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,8,22]]},"reference":[{"issue":"4","key":"pone.0309394.ref001","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/s41571-023-00734-5","article-title":"Cancer-associated cachexia\u2014understanding the tumour macroenvironment and microenvironment to improve management","volume":"20","author":"JM Argil\u00e9s","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"issue":"9","key":"pone.0309394.ref002","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1042\/BCJ20201009","article-title":"Cancer cachexia: molecular mechanism and pharmacological management","volume":"478","author":"Y Li","year":"2021","journal-title":"Biochem J"},{"issue":"16","key":"pone.0309394.ref003","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22168491","article-title":"Cancer Cachexia: Its Mechanism and Clinical Significance.","volume":"22","author":"H Nishikawa","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"5","key":"pone.0309394.ref004","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1002\/jcsm.13323","article-title":"Diagnosis and outcomes of cachexia in Asia: Working Consensus Report from the Asian Working Group for Cachexia","volume":"14","author":"H Arai","year":"2023","journal-title":"J Cachexia Sarcopenia Muscle"},{"issue":"3","key":"pone.0309394.ref005","doi-asserted-by":"crossref","first-page":"227","DOI":"10.4103\/apjon.apjon_68_18","article-title":"Evaluation of the True Endpoint of Clinical Trials for Cancer Cachexia","volume":"6","author":"T. 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