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
英文原题:CS1 Expression Pattern in NK Cells and Correlated Factors in Plasma Cell dyscrasias: Implications for Elotuzumab Therapy and CAR-T Efficacy.
CS1 Expression Pattern in NK Cells and Correlated Factors in Plasma Cell dyscrasias: Implications for Elotuzumab Therapy and CAR-T Efficacy.
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单独使用 elotuzumab 未显示明显抗肿瘤作用,靶向 CS1 的嵌合抗原受体(CAR)T 细胞治疗进展也相对缓慢。
本研究回顾分析 236 例多发性骨髓瘤(MM)患者和 30 例其他浆细胞疾病(PCD)患者,采用多参数流式细胞术评估 NK 细胞、淋巴细胞和单克隆浆细胞中的 CS1 表达,并进一步探索 elotuzumab 的抗肿瘤应用。与其他 PCD 患者相比,MM 患者浆细胞中的 CS1 表达水平显著较高,而淋巴细胞和 NK 细胞中无显著差异。在 MM 和其他 PCD 患者中,浆细胞 CS1 表达均显著高于 NK 细胞和淋巴细胞。单变量和多变量分析显示,血浆细胞 CS1 表达与 NK 细胞中 CS1 表达显著相关(r=0.60,P<0.001;r=0.79,P<0.001)。细胞遗传学异常、疾病进展和生存等因素均与 NK 细胞 CS1 表达无关。
此外,本研究显示,elotuzumab 可显著增强 NK 细胞对非浆细胞肿瘤和浆细胞肿瘤的细胞毒作用,且不依赖于肿瘤 CS1 表达水平。这凸显 elotuzumab 联合 NK 细胞治疗多种肿瘤类型的潜力。
Treatment with elotuzumab alone has no discernible antitumor effect and progress in chimeric antigen receptor T cells (CAR-T) therapy targeting CS1 is relatively slow. A retrospective analysis was performed on 236 patients with multiple myeloma (MM) and 30 patients with other plasma cell dyscrasias (PCDs). CS1 expression in NK cells, lymphocytes, and monoclonal plasma cells was assessed using multiparameter flow cytometry.
Furthermore, new explorations were undertaken regarding the antitumor applications of elotuzumab. Patients with MM had significantly higher CS1 expression levels in plasma cells than other patients with PCDs, with no significant differences between lymphocytes and NK cells. In both patients with MM and other PCDs, CS1 expression was significantly higher in plasma cells than in NK cells and lymphocytes.
Univariate and multivariate analyses revealed a significant correlation between CS1 expression in plasma (r = 0. 60; P < 0. 001) and NK (r = 0. 79; P < 0. 001) cells. Factors such as cytogenetic abnormalities, disease progression, and survival were not associated with CS1 expression in NK cells.
Moreover, this study showed that elotuzumab strongly increases the cytotoxicity of NK cells against non-plasma and plasma tumor cells independent of their CS1 expression level. This underscores the potential of elotuzumab in combination with NK cells as an effective therapeutic strategy against a broad spectrum of tumor types.
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