Data from Genetic Modification of T Cells Redirected toward CS1 Enhances Eradication of Myeloma Cells

التفاصيل البيبلوغرافية
العنوان: Data from Genetic Modification of T Cells Redirected toward CS1 Enhances Eradication of Myeloma Cells
المؤلفون: Jianhua Yu, Craig C. Hofmeister, Xue-Feng Bai, Xiaoming He, Steven M. Devine, Qi-En Wang, Chang-Hyuk Kwon, Ling Yi, Tiffany Hughes, Yong Peng, Jianying Zhang, Youcai Deng, Shun He, Jianhong Chu
بيانات النشر: American Association for Cancer Research (AACR), 2023.
سنة النشر: 2023
الوصف: Purpose: Our goal is to test whether CS1 could be targeted by chimeric antigen receptor (CAR) T cells to treat multiple myeloma (MM).Experimental Design: We generated a retroviral construct of a CS1-specific CAR and engineered primary human T cells expressing the CAR. We then tested the capacity of CS1–CAR T cells to eradicate human MM tumor cells in vitro, ex vivo, and in vivo using orthotopic MM xenograft mouse models.Results:In vitro, compared with mock-transduced T cells, upon recognizing CS1-positive MM cells, CS1–CAR-transduced T cells secreted more IFN-γ as well as interleukin (IL)-2, expressed higher levels of the activation marker CD69, showed higher capacity for degranulation, and displayed enhanced cytotoxicity. Ectopically forced expression of CS1 in MM cells with low CS1 expression enhanced recognition and killing by CAR T cells. Ex vivo, CS1–CAR T cells also showed similarly enhanced activities when responding to primary MM cells. More importantly, in orthotopic MM xenograft mouse models, adoptive transfer of human primary T cells expressing CS1–CAR efficiently suppressed the growth of human MM.1S and IM9 myeloma cells and significantly prolonged mouse survival.Conclusions: CS1 is a promising antigen that can be targeted by CAR-expressing T cells for treatment of MM. Clin Cancer Res; 20(15); 3989–4000. ©2014 AACR.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::af5f95c239099586c82ef9d24fa24868
https://doi.org/10.1158/1078-0432.c.6522267.v1
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....af5f95c239099586c82ef9d24fa24868
قاعدة البيانات: OpenAIRE