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Cancer cachexia is an underrecognized syndrome that impacts ~50% of all cancer patients and accounts for up to ~20% of all cancer deaths. Lung cancer remains one of the deadliest cancers in the United States with an estimated 137\u2009000 deaths in the year 2021 alone. Lung cancer is highly comorbid with cancer cachexia. Pre\u2010clinical models are heavily relied upon to study both lung cancer and cancer cachexia; however, there is a need to develop novel models to study the relationship between the two diseases. We therefore characterized the cachexia phenotype in the CMT\u2010167 syngeneic lung cancer model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male C57BL6\/J mice, aged 8\u201310\u2009weeks, were administered an intramuscular (IM) injection of either 0.5\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> CMT\u2010167 cells or vehicle. Clinically relevant features of cancer cachexia were assessed 23\u2009days after CMT\u2010167 cell administration in tumour bearing mice by assessment of terminal skeletal muscle and adipose tissue mass, gastrocnemius myofiber cross sectional area (CSA), circulating biomarkers of cachexia, and skeletal muscle E3 ubiquitin ligase mRNA. A single intravenous dose pharmacokinetic study of pembrolizumab was completed to assess tumour status influence upon antibody pharmacokinetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to tumour free (TF) mice, we observed lower terminal tumour\u2010adjusted bodyweight, adipose tissue mass, gastrocnemius mass, quadriceps mass, and gastrocnemius myofiber CSA. CMT\u2010167 tumour bearing (TB) mice did not lose bodyweight relative to starting weight, but instead failed to gain as much weight as TF controls. CMT\u2010167 TB mice exhibited increased concentrations of circulating markers of cachexia and muscle wasting, such as IL\u20106 and TNF\u2010<jats:italic>\u03b1<\/jats:italic>, although there was no difference in transcription of E3 ubiquitin ligases <jats:italic>Trim63<\/jats:italic> (MuRF\u20101) and <jats:italic>Fbxo32<\/jats:italic> (atrogin\u20101) in skeletal muscle compared to TF mice. CMT\u2010167\u2009TB mice exhibited increased catabolic clearance (CL) of the human IgG4 anti\u2010PD\u20101, pembrolizumab, agreeing with published literature showing increased CL of immune checkpoint inhibitors in cachectic populations. Comparing the IM CMT\u2010167 model to historical data with the well\u2010established IM Lewis Lung Carcinoma model, CMT\u2010167\u2009TB mice displayed a less severe cachectic phenotype in terms of bodyweight and skeletal muscle effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The IM CMT\u2010167 model is a syngeneic lung cancer model of mild cachexia. CMT\u2010167\u2009TB mouse is a novel model in which to study cancer cachexia induction, skeletal muscle atrophy and immune checkpoint inhibitor clearance mechanisms in the context of lung cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/rco2.117","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T07:50:12Z","timestamp":1738914612000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Intramuscular CMT\u2010167 Tumours Produce a Mild Cachexia Phenotype in C57BL\/6J Mice"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6506-077X","authenticated-orcid":false,"given":"Bryan\u00a0C.","family":"Remaily","sequence":"first","affiliation":[{"name":"Division of Pharmaceutics and Pharmacology, College of Pharmacy The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trang\u00a0T.","family":"Vu","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics and Pharmacology, College of Pharmacy The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Thomas","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics and Pharmacology, College of Pharmacy The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyeongmin","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics and Pharmacology, College of Pharmacy The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camille","family":"Stanton","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics and Pharmacology, College of Pharmacy The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiliang","family":"Xie","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics and Pharmacology, College of Pharmacy The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Granchie","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics and Pharmacology, College of Pharmacy The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Millennium","family":"Manna","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics and Pharmacology, College of Pharmacy The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Gregorevic","sequence":"additional","affiliation":[{"name":"Centre for Muscle Research, Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences The University of Melbourne  Parkville Victoria Australia"},{"name":"Department of Neurology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaokui","family":"Mo","sequence":"additional","affiliation":[{"name":"Center for Biostatistics, Department of Biomedical Informatics, College of Medicine The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeovanna","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, College of Medicine The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill\u00a0A.","family":"Rafael\u2010Fortney","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, College of Medicine The Ohio State University  Columbus Ohio USA"},{"name":"Davis Heart and Lung Research Institute, College of Medicine The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel\u00a0K.","family":"Kulp","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics and Pharmacology, College of Pharmacy The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Latha\u00a0P.","family":"Ganesan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dwight\u00a0H.","family":"Owen","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology The Ohio State University James Comprehensive Cancer Center  Columbus Ohio USA"},{"name":"Division of Gastroenterology, Hepatology &amp; 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