产品号 #17849_C
免疫磁珠正选细胞分选试剂盒
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总览
EasySep™人CD271正选试剂盒 II 专为从人新鲜骨髓中通过正选分离CD271+细胞而设计。目的细胞被识别CD271的抗体四聚体复合物和葡聚糖包被的磁珠标记，试剂盒中还含有人Fc受体的结合抗体，可最大程度减少非特异性结合。通过EasySep™磁极进行无柱分选，标记的细胞保留在分离管中，未被标记的细胞倒出即可。CD271抗原表达于多种细胞类型，包括间充质干细胞和祖细胞（MSCs）。
该产品可替代EasySep™人CD271正选试剂盒 (产品号 #18659) 以进行更快的细胞分选。
磁体兼容性
EasySep™ Magnet (Catalog #18000)
亚型
细胞分选试剂盒
细胞类型
间充质干/祖细胞
种属
人
样本来源
Bone Marrow
筛选方法
Positive
应用
细胞分选
品牌
EasySep
研究领域
干细胞生物学
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Applications
This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.
Resources and Publications
Educational Materials (6)
Publications (1)
Both APRIL and antibody-fragment-based CAR T cells for myeloma induce BCMA downmodulation by trogocytosis and internalization. Journal for immunotherapy of cancer 2022 nov
Abstract
BACKGROUND Chimeric antigen receptor (CAR) T cell therapy targeting B cell maturation antigen (BCMA) on multiple myeloma (MM) produces fast but not long-lasting responses. Reasons for treatment failure are poorly understood. CARs simultaneously targeting two antigens may represent an alternative. Here, we (1) designed and characterized novel A proliferation inducing ligand (APRIL) based dual-antigen targeting CARs, and (2) investigated mechanisms of resistance to CAR T cells with three different BCMA-binding moieties (APRIL, single-chain-variable-fragment, heavy-chain-only). METHODS Three new APRIL-CARs were designed and characterized. Human APRIL-CAR T cells were evaluated for their cytotoxic function in vitro and in vivo, for their polyfunctionality, immune synapse formation, memory, exhaustion phenotype and tonic signaling activity. To investigate resistance mechanisms, we analyzed BCMA levels and cellular localization and quantified CAR T cell-target cell interactions by live microscopy. Impact on pathway activation and tumor cell proliferation was assessed in vitro and in vivo. RESULTS APRIL-CAR T cells in a trimeric ligand binding conformation conferred fast but not sustained antitumor responses in vivo in mouse xenograft models. In vitro trimer-BB$\zeta$ CAR T cells were more polyfunctional and formed stronger immune synapses than monomer-BB$\zeta$ CAR T cells. After CAR T cell-myeloma cell contact, BCMA was rapidly downmodulated on target cells with all evaluated binding moieties. CAR T cells acquired BCMA by trogocytosis, and BCMA on MM cells was rapidly internalized. Since BCMA can be re-expressed during progression and persisting CAR T cells may not protect patients from relapse, we investigated whether non-functional CAR T cells play a role in tumor progression. While CAR T cell-MM cell interactions activated BCMA pathway, we did not find enhanced tumor growth in vitro or in vivo. CONCLUSION Antitumor responses with APRIL-CAR T cells were fast but not sustained. Rapid BCMA downmodulation occurred independently of whether an APRIL or antibody-based binding moiety was used. BCMA internalization mostly contributed to this effect, but trogocytosis by CAR T cells was also observed. Our study sheds light on the mechanisms underlying CAR T cell failure in MM when targeting BCMA and can inform the development of improved treatment strategies.
更多信息
| Species | Human |
|---|---|
| Magnet Compatibility | EasySep™ Magnet (Catalog #18000) |
| Sample Source | Bone Marrow |
| Selection Method | Positive |
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PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED. FOR ADDITIONAL INFORMATION ON QUALITY AT STEMCELL, REFER TO WWW.STEMCELL.COM/COMPLIANCE.
