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Prashant Kapoor, MD, FACP


CD98 Heavy Chain Protein and Myeloma: Preclinical Study of Novel Monoclonal Antibody

By: Victoria Kuhr, BA
Posted: Monday, April 18, 2022

Kana Hasegawa, MD, of Osaka University, Japan, proposed that multiple myeloma may respond to a novel monoclonal antibody (R8H283) that recognizes the universally present protein CD98 heavy chain. Additionally, Dr. Hasegawa and colleagues observed that monoclonal antibodies bonded only to multiple myeloma cells despite the presence of CD98 heavy chain in normal cells. These study findings were published in Science Translational Medicine.

The study screened more than 10,000 monoclonal antibody clones against patient-derived multiple myeloma cells. Of the more than 10,000 monoclonal antibody clones, R8H283 specifically bound with CD98 heavy chain protein in heterodimers with a CD98 light chain (CD98lc), a complex that functions as an amino acid transporter. CD98 heterodimers were abundant on multiple myeloma cells and took up amino acids for constitutive production of immunoglobulin. Although CD98 heterodimers were also present on normal leukocytes, R8H283 did not appear to react with them. The glycoforms of CD98 heavy chains that are present on normal leukocytes were distinct from those present on multiple myeloma cells. The location of these glycoforms may explain the lack of R8H283 reactivity to normal leukocytes, proposed the study authors.

To examine the effectiveness of R8H283, mice were injected with multiple myeloma xenograft models. The investigators found that R8H283 injections prolonged the survival of mice and exerted antimyeloma effects without damaging normal host cells. These findings highlight a potential approach by which cancer-specific conformational epitopes on widely expressed proteins may be identified via the screening of primary tumor samples.

Disclosure: For full disclosures of the study authors, visit

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