{"id":8829,"date":"2025-04-04T14:00:03","date_gmt":"2025-04-04T05:00:03","guid":{"rendered":"https:\/\/www.med.osaka-u.ac.jp\/eng\/?page_id=8829"},"modified":"2025-07-31T13:30:26","modified_gmt":"2025-07-31T04:30:26","slug":"hosen2025-4-4","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2025year\/hosen2025-4-4","title":{"rendered":"Naoki Hosen \u226aHematology and Oncology\u226b <span>Driving the CAR to fight acute myeloid leukemia<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li><a href=\"https:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2025year\/hosen2025-4-4\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p><span class=\"lineFrame\">Nature Cancer<\/span><\/p>\n<p>Researchers from The University of Osaka identify a molecule that can support specific therapeutic targeting of AML with chimeric antigen receptor therapy.<\/p>\n<p class=\"figure\"><a href=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/04\/hosen_efig1.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-8832\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/04\/hosen_efig1-400x300.jpg?_t=1743568257\" alt=\"\" width=\"600\" height=\"451\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/04\/hosen_efig1-400x300.jpg 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/04\/hosen_efig1-768x577.jpg 768w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/04\/hosen_efig1.jpg 900w\" sizes=\"(max-width: 600px) 100vw, 600px\" \/><\/a><br \/>Figure 1.\u00a0Novel CAR T cells and cord blood-derived CAR NK cells for relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation.<br \/>When a patient with KG2032-reactive AML undergoes allogeneic hematopoietic stem cell transplantation from a KG2032-unreactive donor, administration of donor T cells or cord blood-derived NK cells transduced with the KG2032-derived CAR will target the patient&#8217;s AML cells but not the donor-derived normal hematopoietic cells)<\/p>\n<div class=\"TextBlock\">\n<p>One main goal of anti-cancer therapies is to kill tumor cells without affecting the surrounding normal cells. Therefore, many drugs are designed to target tumor-specific antigens, which are molecules only expressed by cancer cells. However, it has proven difficult to identify such specific antigens in certain cancer types, including acute myeloid leukemia (AML).\u00a0\u00a0<\/p>\n<p>AML patients are often treated using allogeneic hematopoietic stem cell transplantation (allo-HCT), where they receive stem cells from a donor. Unfortunately, despite advancements with allo-HCT, many AML patients relapse.\u00a0\u00a0<\/p>\n<p>In a recent article published in <em>Nature Cancer<\/em>, a multi-institutional research team led by The University of Osaka describes how a molecule called HLA-DRB1 can be used as a target for chimeric antigen receptor (CAR)-based therapy for AML. In CAR-based therapy, T cells are engineered to target and kill cells that express a specific molecule. CAR T cells have been highly successful in individuals with B cell leukemia\/lymphoma and multiple myeloma (MM). However, most of the CAR T cell targets currently in clinical trials for AML are also expressed in normal cell types, leading to potential toxicity.\u00a0<\/p>\n<p>\u201cIn our previous work in MM, we screened monoclonal antibodies (mAbs) to identify any that could react with human MM samples but not with normal blood cells,\u201d says Shunya Ikeda, lead author of the study. \u201cWe aimed to use that same strategy to find AML-specific antigens.\u201d\u00a0<\/p>\n<p>The team began screening thousands of mAbs raised against AML cells, narrowing this list down to 32 that bind specifically to AML cells. One mAb, named KG2032, clearly bound to AML cells in over 50% of patient samples tested. Using a sequencing strategy, the researchers determined that KG2032 bound to HLA-DRB1.\u00a0<\/p>\n<p>\u201cInterestingly, we found that KG2032 reacted with a specific HLA-DRB1 subset in which the protein has an amino acid other than aspartic acid in the 86<sup>th<\/sup> position,\u201d explains Naoki Hosen, senior author of the article. \u201cKG2032 would therefore only be reactive in individuals with mismatched HLA-DRB1, meaning the patient carries this amino acid alteration but the allo-HCT donor does not.\u201d\u00a0\u00a0<\/p>\n<p>This finding indicates that HLA-DRB1 can be a potential target in treating certain patients with AML who have relapsed after allo-HCT.\u00a0<\/p>\n<p>The team then engineered KG2032 CAR T cells without the reactive HLA-DRB1 allele to test this finding. The KG2032 CAR T cells displayed strong and specific anti-AML effects <em>in vitro<\/em> with cell culture experiments, as well as <em>in vivo<\/em> with a mouse model. The treated mice did not display any overt signs of toxicity. Engineered cord blood-derived CAR natural killer (NK) cells showed similar results.\u00a0<\/p>\n<p>Overall, these very promising findings indicate that KG2032-derived CAR T or NK cells may be a lifesaving intervention for AML patients who have relapsed following allo-HCT. Clinical trials are currently being planned for both cell types..<\/p>\n<\/div>\n<p>###<\/p>\n<p>The article, \u201cCAR T or NK cells targeting mismatched HLA-DR molecules in acute myeloid leukemia after allogeneic hematopoietic stem cell transplant,\u201d was published in<em> Nature Cancer<\/em> at DOI: <a href=\"https:\/\/www.nature.com\/articles\/s43018-025-00934-1\">10.1038\/s43018-025-00934-1.<\/a><\/p>\n<p><strong>Summary:<\/strong> A multi-institutional team led by The University of Osaka developed a chimeric antigen receptor (CAR) T cell-based strategy for specifically targeting AML cells in patients who relapsed following other treatments. The team identified a monoclonal antibody called KG2032 that reacts with a certain variant of the HLA-DRB1 molecule. KG2032 CAR T cells displayed strong anti-AML effects in a mouse model, and CAR natural killer cells showed similar results. Clinical trials are currently being planned.<\/p>\n<p><strong>Tweet 1<\/strong>: UOsaka researchers find that targeting a specific HLA-DRB1 molecule in acute myeloid leukemia may lead to curative effects in patients who do not respond to other treatments<\/p>\n<p><strong>Tweet 2<\/strong>: UOsaka researchers identify a specific molecular target that may revolutionize the therapeutic landscape for acute myeloid leukem<\/p>\n<p><strong>Primary Keyword<\/strong>: Health and medicine<\/p>\n<p><strong>Additional Keyword<\/strong>: cancer treatments, cancer immunotherapy, chimeric antigen receptor therapy, leukemia, monoclonal antibodies, cell transplantation, mouse models<\/p>\n<p><strong>Method of Research<\/strong>: Experimental study<\/p>\n<p><strong>Subject of Research<\/strong>: Cells<\/p>\n<p class=\"figure\"><a href=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/04\/hosen_efig2.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-8834\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/04\/hosen_efig2-400x300.jpg?_t=1743569666\" alt=\"\" width=\"600\" height=\"451\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/04\/hosen_efig2-400x300.jpg 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/04\/hosen_efig2-768x577.jpg 768w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2025\/04\/hosen_efig2.jpg 900w\" sizes=\"(max-width: 600px) 100vw, 600px\" \/><\/a><br \/>Figure 2.\u00a0Significant anti-tumor effects of KG2032 CAR T\/NK cells<strong><br \/><\/strong>Fluorescence intensity reflects leukemia burden. In the control cell administration group, leukemia progressed over time, but in the KG2032 CAR T\/NK cell administration group, leukemia progression was significantly suppressed.<\/p>\n<div class=\"TextBlock\">\n<p>Title: \u201cCAR T or NK cells targeting mismatched HLA-DR molecules in acute myeloid leukemia after allogeneic hematopoietic stem cell transplant\u201d<\/p>\n<\/div>\n<p>Journal: <em>Nature Cance<\/em><em><br \/><\/em>Authors: Shunya Ikeda <em>et al<\/em>.<br \/>DOI: <a href=\"https:\/\/www.nature.com\/articles\/s43018-025-00934-1\">10.1038\/s43018-025-00934-1<\/a><\/p>\n<p>Japan Society for the Promotion of Science (JSPS),<br \/>Japan Agency for Medical Research and Development (AMED),<br \/>Chemo-Sero- Therapeutic Research Institute,<br \/>Takeda Science Foundation<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese Nature Cancer Researchers from The University of Osaka identify a molecule that can support s [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":8832,"parent":8696,"menu_order":28,"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\/8829"}],"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=8829"}],"version-history":[{"count":9,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8829\/revisions"}],"predecessor-version":[{"id":9192,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8829\/revisions\/9192"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8696"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/8832"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=8829"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}