Antibody candidate could help preserve appetite and muscle strength in patients with cancer

by The Korea Advanced Institute of Science and Technology (KAIST)

edited by Swati Mestri, reviewed by Robert Egan

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In cancer cachexia, patients continue to lose weight, muscle and fat even when they eat. A KAIST research team has developed a therapeutic candidate that blocks a signal responsible for appetite suppression, weight loss and excessive energy expenditure.

In mouse experiments, the candidate restored food intake and reduced muscle and fat loss. The researchers hope it will help cancer patients maintain the physical strength they need to continue treatment.

A research team led by professor Ho Min Kim from the Department of Biological Sciences, in collaboration with a team led by professor Minho Shong of the Graduate School of Medical Science and Engineering (CEO of THOR Therapeutics, a KAIST faculty startup), has developed GB2Ab, an antibody candidate that alleviates cancer cachexia in mice.

The findings are published in the journal Science Advances.

An antibody is a protein that recognizes and binds to a specific substance. The team used this property to block a signaling pathway that contributes to physical wasting and demonstrated therapeutic effects in mice. A therapeutic candidate is a substance being evaluated for its efficacy and safety for potential development into a treatment.

Blocking the signal behind cancer-related wasting

Cancer cachexia differs from weight loss caused simply by poor appetite or reduced food intake. It is a complication in which cancer alters the way the body uses nutrients and energy, leading to the loss of both muscle and fat. Because nutritional support alone is often insufficient to reverse this process, cachexia can make it difficult for patients to carry out daily activities and continue cancer treatment.

One of the mediators involved in this process is a protein called GDF15. Cancer or severe stress can increase GDF15 levels in the blood. GDF15 then binds to the GFRAL receptor in the brainstem, located in the hindbrain, triggering a signal that reduces appetite and affects energy use. A receptor is a protein that receives a signal by binding to a specific substance. In this pathway, GDF15 sends the signal and GFRAL receives it.

The team focused on blocking this receptor with an antibody. Rather than binding directly to GDF15 in the blood, this approach targets GFRAL, the receptor that receives the signal. The antibody GB2Ab binds tightly to the receptor and suppresses the signaling involved in appetite loss and excessive energy expenditure.

The researchers also analyzed the three-dimensional structure of the antibody-receptor complex. They identified where and how the antibody binds, revealing its mechanism of action. Based on these findings, they modified the antibody to improve its production efficiency and stability.

Treated mice regained weight and strength

The team tested the antibody in mice that had developed cancer cachexia after being implanted with colorectal cancer cells. Mice treated with the antibody showed restored food intake, and their body weight, excluding tumor weight, was about 20% higher than that of untreated mice. Muscle and fat loss were also reduced.

Grip strength, a measure of the ability to grasp an object, also improved. Treated mice showed about 30% greater grip strength than untreated mice, reaching about 90% of the level observed in healthy mice. These results show that the antibody improved not only body weight but also muscle function.

Antibody treatment also reduced excessive activity in the sympathetic nervous system, which regulates the body's stress response and energy use. This finding indicates that, in addition to increasing food intake, the antibody can reduce excessive energy expenditure.

Human safety and efficacy remain unproven

When healthy mice received a high dose of 100 mg per kilogram of body weight, no apparent abnormalities in body weight or food intake were observed. However, further testing, including clinical trials in humans, is needed to establish the antibody's safety and efficacy before it can be developed into a treatment for patients.

The candidate is intended to alleviate cancer-related wasting rather than shrink the tumor itself. The team expects that, when used alongside existing cancer drugs, it could help patients maintain body weight and muscle strength as they continue treatment. Follow-up studies are underway to examine its effects in combination with immunotherapy.

"This study is significant because we developed an antibody that blocks a signal involved in cancer cachexia, identified its mechanism of action and demonstrated its effects in mice," said Kim. He added that the team aims to develop it into a therapy that not only restores appetite but also reduces muscle and fat loss and preserves physical function, helping cancer patients maintain the strength they need to continue treatment.

"Building on our drug development expertise, we are accelerating further development," said Shong. He added that the team aims to develop the candidate into a therapy that improves cancer patients' quality of life and helps them continue cancer treatment.

Publication details

Sohyun Kim et al., Induced-fit anti-GFRAL antibody ameliorates cancer cachexia and attenuates sympathetic outflow in tumor-bearing mice, Science Advances (2026). DOI: 10.1126/sciadv.aee5992

Journal information: Science Advances

Key medical concepts

Growth Differentiation Factor 15

Clinical categories

OncologyClinical pharmacologyCommon illnesses & Prevention Provided by The Korea Advanced Institute of Science and Technology (KAIST) Who's behind this story?

Swati Mestri

Swati Mestri holds a bachelor's degree in Electronics Engineering and has worked as a content editor since 2019. She has experience editing research documents across technology, health care, and materials science, and has a particular interest in technology and space. Full profile →

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