{"id":7023,"date":"2022-02-28T14:32:47","date_gmt":"2022-02-28T05:32:47","guid":{"rendered":"https:\/\/www.med.osaka-u.ac.jp\/eng\/?page_id=7023"},"modified":"2022-08-19T14:50:01","modified_gmt":"2022-08-19T05:50:01","slug":"hosen2022-2-28","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2022year\/hosen2022-2-28","title":{"rendered":"Kana Hasegawa, Naoki Hosen \u226aCellular Immunotherapy, Hematology and Oncology\u226b <span>A myeloma-targeting monoclonal antibody offers new hope for treating multiple myeloma<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li><a href=\"https:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2022year\/hosen2022-2-28\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p><em>Science Translational Medicine<\/em><\/p>\n<p><em>Researchers from Osaka University find a monoclonal antibody that recognizes a cancer-specific surface antigen in a ubiquitous protein with exciting therapeutic potential<\/em><\/p>\n<p class=\"figure\"><a href=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2022\/02\/hosen_fig.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-7049 size-medium\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2022\/02\/hosen_fig-400x300.jpg?_t=1645511711\" alt=\"\" width=\"400\" height=\"300\" \/><\/a><\/p>\n<p>Figure. Summary of the research\u3000<\/p>\n<p>Multiple myeloma (MM) is a largely incurable cancer of plasma cells with an extremely poor prognosis. However, investigators from Japan have recently found that a common component of amino acid transporters, CD98 heavy chain, represents an effective monoclonal antibody target in treating MM.<\/p>\n<p>In a study published this month in <em>Science Translational Medicine<\/em>, researchers from Osaka University have revealed a new approach that involves extensive screening of monoclonal antibody clones against primary human tumor samples. The aim was to identify cancer-specific conformational epitopes on ubiquitous proteins that cannot be identified by transcriptome or proteome analyses.<\/p>\n<p>Some patients with MM show relapse in disease often due to immune-evading mutations that arise, making the cancer cells resistant to treatment. New target antigens are therefore urgently needed to develop a multi-targeted approach that can circumvent immune evasion and thereby avoid relapse of disease.<\/p>\n<p>Extensive previous efforts have focused on targeting cancer-specific cell surface antigens identified by transcriptome or proteome analyses. But these efforts may have missed cancer-specific antigen epitopes formed by covalent, enzymatic modification of proteins (i.e., posttranslational modifications), such as glycosylation, or conformational changes. To widen the search for novel target antigens, Hasegawa and colleagues screened for cancer-specific monoclonal antibodies and then characterized their target-presenting antigens.<\/p>\n<p>\u201cBy screening over 10,000 monoclonal antibody clones raised against MM cells, we identified R8H283, a monoclonal antibody that recognizes the CD98 heavy chain protein, which is part of an amino acid transporter,\u201d says lead author of the study Kana Hasegawa. \u201cDespite the CD98 heavy chain being present on all cells, the antibody only bound to MM cells. This selectivity may reflect the differing glycosylation patterns between normal cells and MM cells.\u201d<\/p>\n<p>In-depth analysis of the R8H283 antibody revealed specific binding to CD98 heterodimers, not CD98 heavy chain monomers. Heterodimer complexes, comprising the CD98 heavy chain and light chain, modulate the uptake of amino acids for the production of immunoglobulin. \u201cInterestingly, the glycoforms of CD98 heavy chain in the heterodimers present on normal leukocytes were distinct from those present on MM cells, which we think explains the lack of R8H283 reactivity to normal leukocytes,\u201d explains Naoki Hosen, senior author. \u201cThis is significant because it means that R8H283 antibody can exert anti-MM effects without damaging normal host cells.\u201d<\/p>\n<p>To assess the effectiveness of the R8H283 antibody in an animal model, the researchers employed a mouse MM xenograft model. They found that R8H283 injections prolonged the survival of mice. This confirmed that R8H283 is a candidate for monoclonal antibody-based therapy for MM.<\/p>\n<p>Taken together, these findings highlight an effective approach by which cancer-specific conformational epitopes on widely expressed proteins, which are unable to be detected by transcriptome or proteome analyses, may be identified via the screening of primary tumor samples. This methodology may be useful in broadening the array of cancer-specific surface antigens available for future drug development.<\/p>\n<p>###<\/p>\n<p>The article, \u201cSelective targeting of multiple myeloma cells with a monoclonal antibody recognizing the ubiquitous protein CD98 heavy chain,\u201d was published in <em>Science Translational Medicine<\/em> at DOI: https:\/\/doi.org\/10.1126\/scitranslmed.aax7706<\/p>\n<p><strong>Summary: <\/strong>Researchers from Osaka University performed extensive screening of primary tumor samples to identify a monoclonal antibody that recognizes a cancer-specific surface antigen on multiple myeloma (MM) cells. This antibody selectively targets MM cells expressing the ubiquitous protein CD98 heavy chain of amino acid transporters without damaging normal host cells and therefore represents a promising, potential anti-MM therapeutic agent.<\/p>\n<p><strong>Tweet:<\/strong>\u00a0Is multiple myeloma incurable? A monoclonal antibody offers new hope for treatment<\/p>\n<p><strong>Primary Keyword:<\/strong>\u00a0Health and medicine<br \/><strong>Additional Keywords:\u00a0<\/strong>Cancer, Multiple myeloma, Antibody therapy<\/p>\n<p><strong>Method of Research:<\/strong> Experimental study<\/p>\n<p><strong>Subject of Research:<\/strong> Human tissue samples<\/p>\n<p>Title: \u201cSelective targeting of multiple myeloma cells with a monoclonal antibody recognizing the ubiquitous protein CD98 heavy chain\u201d<br \/>Journal: <em>Science Translational Medicine<\/em><em><br \/><\/em>Authors: Kana Hasegawa, Shunya Ikeda, Moto Yaga, Kouki Watanabe Rika Urakawa, Akie Iehara, Mai Iwai, Seishin Hashiguchi, Soyoko Morimoto, Fumihiro Fujiki, Hiroko Nakajima, Jun Nakata, Sumiyuki Nishida, Akihiro Tsuboi, Yoshihiro Oka, Satoshi Yoshihara, Masahiro Manabe, Hiroyoshi Ichihara, Atsuko Mugitani, Yasutaka Aoyama, Takafumi Nakao, Asao Hirose, Masayuki Hino, Shiho Ueda, Takashi Masuko, Katsuto Takenaka, Koichi Akashi, Takahiro Maruno, Susumu Uchiyama, Shinji Takamatsu, Naoki Wada, Eiichi Morii, Shushi Nagamori, Daisuke Motooka, Yoshikatsu Kanai, Yusuke Oji, Tomoyoshi Nakagawa, Noriyuki Kijima, Haruhiko Kishima, Atsuyo Ikeda, Takayuki Ogino, Yasushi Shintani, Tateki Kubo, Emiko Mihara, Kosuke Yusa, Haruo Sugiyama, Junichi Takagi, Eiji Miyoshi, Atsushi Kumanogoh, Naoki Hosen<br \/>DOI: <a href=\"https:\/\/doi.org\/10.1126\/scitranslmed.aax7706\">10.1126\/scitranslmed.aax7706<\/a><\/p>\n<p>Funded by: Japan Society for the Promotion of Science<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese Science Translational Medicine Researchers from Osaka University find a monoclonal antibody t [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":7055,"parent":6951,"menu_order":188,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/7023"}],"collection":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/comments?post=7023"}],"version-history":[{"count":23,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/7023\/revisions"}],"predecessor-version":[{"id":7551,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/7023\/revisions\/7551"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/6951"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/7055"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=7023"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}