KAIST Develops Antibody Candidate to Help Preserve Appetite and Muscle Strength in Patients with Cancer (IMAGE)

The Korea Advanced Institute of Science and Technology (KAIST)

KAIST Develops Antibody Candidate to Help Preserve Appetite and Muscle Strength in Patients with Cancer

Caption

Figure 4. Discovery, mechanism of action, and therapeutic efficacy of the GFRAL antibody against cancer cachexia

  1. The researchers discovered a monoclonal antibody (GB2Ab) that targets the GFRAL protein. By determining the crystal structure of the GFRAL-antibody complex, they found that the antibody binds through a distinctive induced-fit mechanism in which antibody binding changes the structure of GFRAL.
  2. Cell-based experiments showed that GB2Ab directly blocks the site where GFRAL binds to RET, thereby inhibiting GDF15-GFRAL-RET signaling. Using the structural information, the team humanized the antibody and developed the therapeutic candidate 3D-hz-GB2Ab.

When 3D-hz-GB2Ab was administered to mice with cancer cachexia, food intake, body weight, and muscle strength recovered, and muscle and fat loss was reduced, confirming its therapeutic efficacy against cancer cachexia.

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KAIST

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