Possible treatment of human multiple myeloma found

Posted by Ellen Burns on March 29th, 2022

Multiple myeloma is an essentially incurable plasma cell cancer with a very poor prognosis for patients; however, in a recent study published in Science Translational Medicine entitled \"Selective targeting of multiple myeloma cells with a monoclonal antibody recognizing the protein CD98 heavy chain,\" scientists from Osaka University in Japan have discovered the CD98 heavy chain, a common component of a common amino acid transporter, which may represent an effective monoclonal antibody with promise for the treatment of multiple myeloma.

In the study, the researchers propose a new method that mainly involves extensive screening of monoclonal antibodies against primary human tumor samples with the aim of identifying cancer-specific conformational epitopes throughout the protein that cannot be identified by transcriptome or proteome analysis. Some patients with multiple myeloma often relapse due to the emergence of immune escape mutations, which makes cancer cells in the body resistant to therapy; therefore, researchers urgently need a new target antigen to develop a multi-targeted method, so as to avoid immune escape and avoid disease recurrence.

In previous studies, researchers focused on cancer-specific cell surface antigens by transcriptome or proteome analysis, but these studies may have missed cancer-specific epitopes formed by covalent and enzymatic modifications of proteins (such as post-translational modifications), such as glycosylation or conformational changes; in order to expand the search for new target antigens, researchers Hasegawa and colleagues screened cancer-specific monoclonal antibodies and then characterized the antigens they targeted for presentation.

\"By screening more than 10,000 monoclonal antibodies against multiple myeloma cells, we identified R8H283, a specific monoclonal protein that recognizes the CD98 heavy chain protein, which is part of the amino acid transporter,\" said researcher Kana Hasegawa. The cloned antibody binds only to multiple myeloma cells, although the CD98 heavy chain is present in all cells, and this selectivity may reflect the different glycosylation patterns between normal and multiple myeloma cells.

In-depth analysis of the R8H283 antibody revealed specific binding to the CD98 isoform, but not the CD98 heavy chain monomer. Heterodimeric complexes composed of CD98 heavy and light chains may modulate the uptake of amino acids required for immunoglobulin production. Interestingly, the glycan isoform of CD98 heavy chain in heterodimers present on normal leukocytes is different from that present in multiple myeloma cells, which may explain the lack of reactivity of R8H283 on normal leukocytes; This is interesting because it means that the R8H283 antibody may be able to exert an anti-multiple myeloma effect without damaging normal host cells.

To assess the efficacy of the R8H283 antibody in animal models, the researchers used a mouse multiple myeloma xenograft model and found that injection of R8H283 may prolong the survival time of mice, which may confirm that R8H283 can be used as a candidate for monoclonal antibody-based therapy for the treatment of multiple myeloma. In summary, in this study, the researchers found a particularly effective method that may identify cancer-specific conformational epitopes on widely expressed proteins by screening primary tumor samples that cannot be detected by transcriptome or proteome analysis, and this method may help expand microarray studies of cancer-specific surface antigens that can be used for future drug discovery.

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Ellen Burns

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Ellen Burns
Joined: November 1st, 2019
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