Research Project
10244794
Therapeutic antibody for cancer-associated cachexia Abstract Cachexia is a debilitating, wasting disease, characterized by loss of appetite, skeletal muscle, and fat mass. Cancer-associated cachexia constitutes a major unmet medical need, as 80% of patients with advanced cancers exhibit cachexia, and 25% of cancer-related mortalities are derived from cachexia rather than direct tumor burden. Cachexic patients are less tolerant to radiotherapy, chemotherapy, pharmacotherapy, and surgery. For this reason, they receive lower doses, reduced duration of treatment, or are not eligible for treatment, indirectly increasing mortality. There is currently no approved treatment for cachexia. Growth differentiation factor 15 (GDF15) is well documented as a critical mediator of body weight loss, and high GDF15 levels are associated with many cancers. Administration of GDF15 causes weight loss in mice, rats, and primates while blocking GDF15 in models of tumor-associated cachexia rapidly reverses weight loss. We present a high-affinity chimeric monoclonal antibody that neutralizes GDF15 in animal models of tumor-associated cachexia. During this Phase 1 project, we will humanize this lead antibody and demonstrate its equivalence to the parent antibody. Phase 2 studies will advance preclinical testing, including pharmacokinetics and toxicology, in preparation for an IND. The therapeutic antibody to be developed in this project will directly block a major cause of cachexia to enable optimal cancer therapy in cachexic patients.
