CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CD229 与 RASAL3 相互作用激活多发性骨髓瘤增殖中的 RAS/ERK 通路
英文原题：CD229 interacts with RASAL3 to activate RAS/ERK pathway in multiple myeloma proliferation.
查看英文原题
CD229 interacts with RASAL3 to activate RAS/ERK pathway in multiple myeloma proliferation.
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中文摘要
多发性骨髓瘤（MM）是一种无法治愈的浆细胞恶性肿瘤，而 CAR-T 疗法为 MM 的治疗提供了新方向。近年来，信号淋巴细胞激活分子家族3（CD229），一种属于信号淋巴细胞激活分子家族（SLAMF）的细胞表面免疫受体，正逐渐成为 MM 中 CAR-T 治疗的靶点。
然而，CD229 在 MM 中的明确作用仍不清晰。在本研究中，通过分析 MM 临床数据库发现，CD229 表达升高的 MM 患者预后较差。
此外，CD229 在体外以及体内异种移植小鼠模型中均促进 MM 细胞增殖。机制研究揭示，CD229 通过调控 RAS/ERK 信号通路促进 MM 细胞增殖。
进一步探索采用免疫共沉淀结合质谱分析，鉴定出 RASAL3 是 CD229 的重要下游蛋白。此外，我们开发了一种共培养方法结合免疫荧光实验，证实细胞间酪氨酸磷酸化介导的 CD229 自激活通过与 RASAL3 相互作用激活 RAS/ERK 信号通路。
综上所述，这些发现不仅证明了 CD229 在 MM 细胞增殖中的致癌作用，也阐明了 CD229 作为 MM 治疗有前景的潜在靶点的可能性。
展开英文摘要原文
Multiple myeloma (MM) is an incurable plasma cell malignancy, while CAR-T therapy offers a new direction for the treatment of MM. Recently, signaling lymphocytic activation molecule family 3 (CD229), a cell surface immune receptor belonging to the signaling lymphocyte activating molecule family (SLAMF), is emerging as a CAR-T therapeutic target in MM.
However, a clear role of CD229 in MM remains elusive. In this study, MM patients with elevated CD229 expression achieved poor prognosis by analyzing MM clinical databases.
In addition, CD229 promoted MM cell proliferation in vitro as well as in xenograft mouse model in vivo . Mechanism study revealed that CD229 promoted MM cell proliferation by regulating the RAS/ERK signaling pathway.
Further exploration employed co-immunoprecipitation coupled with mass spectrometry to identify RASAL3 as an important downstream protein of CD229.
Additionally, we developed a co-culture method combined with the immunofluorescence assay to confirm that intercellular tyrosine phosphorylation mediated self-activation of CD229 to activate RAS/ERK signaling pathway via interacting with RASAL3. Taken together, these findings not only demonstrate the oncogenic role of CD229 in MM cell proliferation, but also illustrate the potential of CD229 as a promising therapeutic target for MM treatment.
论文信息
- 作者
- Lin Z、Tang X、Cao Y、Yang L、Jiang M、Li X、Min J、Chen B
- 单位
- Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Aging2022 Nov 28
- 原文标识
- PubMed 36445333 · DOI 10.18632/aging.204405
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