Aintzane Zabaleta, Laura Blanco, Peter S Kim, Kamlesh Bisht, Hongfang Wang, Helgi Van de Velde, Marta Lasa, Luis-Esteban Tamariz-Amador, Paula Rodriguez-Otero, Jesús San-Miguel, Bruno Paiva, Esperanza Martín-Sánchez
{"title":"一种 CD38/CD3xCD28 三特异性 T 细胞吸引剂,可作为抗 CD38 单克隆抗体复发和/或难治性多发性骨髓瘤患者的潜在活性药物。","authors":"Aintzane Zabaleta, Laura Blanco, Peter S Kim, Kamlesh Bisht, Hongfang Wang, Helgi Van de Velde, Marta Lasa, Luis-Esteban Tamariz-Amador, Paula Rodriguez-Otero, Jesús San-Miguel, Bruno Paiva, Esperanza Martín-Sánchez","doi":"10.1111/bjh.19784","DOIUrl":null,"url":null,"abstract":"<p><p>There is accumulating evidence of BCMA and GPRC5D loss after treatment with T-cell redirecting therapies in patients with relapsed/refractory multiple myeloma (RRMM). While complete CD38 loss is not observed upon relapses after treatment with anti-CD38 monoclonal antibodies (mAb), there is downregulation of surface CD38 expression and decreased number and function of NK cells, which renders these patients resistant to retreatment with anti-CD38 mAb. Here, we provide preclinical evidence that RRMM patients previously exposed to anti-CD38 mAb could benefit from T-cell-based immunotherapy that depend less on CD38 antigen density and NK-cell activity, such as the novel CD38/CD3xCD28 trispecific T-cell engager, SAR442257.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A CD38/CD3xCD28 trispecific T-cell engager as a potentially active agent in multiple myeloma patients relapsed and/or refractory to anti-CD38 monoclonal antibodies.\",\"authors\":\"Aintzane Zabaleta, Laura Blanco, Peter S Kim, Kamlesh Bisht, Hongfang Wang, Helgi Van de Velde, Marta Lasa, Luis-Esteban Tamariz-Amador, Paula Rodriguez-Otero, Jesús San-Miguel, Bruno Paiva, Esperanza Martín-Sánchez\",\"doi\":\"10.1111/bjh.19784\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>There is accumulating evidence of BCMA and GPRC5D loss after treatment with T-cell redirecting therapies in patients with relapsed/refractory multiple myeloma (RRMM). While complete CD38 loss is not observed upon relapses after treatment with anti-CD38 monoclonal antibodies (mAb), there is downregulation of surface CD38 expression and decreased number and function of NK cells, which renders these patients resistant to retreatment with anti-CD38 mAb. Here, we provide preclinical evidence that RRMM patients previously exposed to anti-CD38 mAb could benefit from T-cell-based immunotherapy that depend less on CD38 antigen density and NK-cell activity, such as the novel CD38/CD3xCD28 trispecific T-cell engager, SAR442257.</p>\",\"PeriodicalId\":135,\"journal\":{\"name\":\"British Journal of Haematology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-09-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"British Journal of Haematology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/bjh.19784\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"British Journal of Haematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/bjh.19784","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
A CD38/CD3xCD28 trispecific T-cell engager as a potentially active agent in multiple myeloma patients relapsed and/or refractory to anti-CD38 monoclonal antibodies.
There is accumulating evidence of BCMA and GPRC5D loss after treatment with T-cell redirecting therapies in patients with relapsed/refractory multiple myeloma (RRMM). While complete CD38 loss is not observed upon relapses after treatment with anti-CD38 monoclonal antibodies (mAb), there is downregulation of surface CD38 expression and decreased number and function of NK cells, which renders these patients resistant to retreatment with anti-CD38 mAb. Here, we provide preclinical evidence that RRMM patients previously exposed to anti-CD38 mAb could benefit from T-cell-based immunotherapy that depend less on CD38 antigen density and NK-cell activity, such as the novel CD38/CD3xCD28 trispecific T-cell engager, SAR442257.
期刊介绍:
The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.