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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Expression levels and patterns of B-cell maturation antigen in newly diagnosed and relapsed multiple myeloma patients from Indian subcontinent.
Expression levels and patterns of B-cell maturation antigen in newly diagnosed and relapsed multiple myeloma patients from Indian subcontinent.
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我们证明,BCMA/CD269 在大多数 MM 患者诊断时和复发时的 aPCs 中高表达。因此,BCMA 是印度 MM 患者治疗的一个有价值的靶点。
许多新疗法正在被评估用于治疗多发性骨髓瘤(MM)。细胞表面蛋白B细胞成熟抗原(BCMA,CD269)最近已成为MM中CAR-T 细胞和单克隆抗体疗法的有希望的靶点。然而,来自印度次大陆的骨髓瘤患者中BCMA表达模式的知识仍然缺乏。我们对印度MM患者异常浆细胞(aPC)上的BCMA表达模式进行了深入研究。
我们研究了217例MM患者的BM样本(211例新诊断和6例复发)和20例对照样本,患者中位年龄为56岁(范围30-78岁,男女比例2.29),并评估了CD269(克隆号19f2)在MM患者aPCs和对照(未受累分期骨髓样本)正常PCs(nPC)中的表达水平/模式,采用多色流式细胞术(MFC)。CD269的表达水平确定为PCs中CD269的平均荧光强度(MFI-R)与非B淋巴细胞的比值,表达模式(均一/异质)确定为免疫荧光变异系数(CVIF)。
CD269阳性异常浆细胞占总浆细胞的中位(范围)百分比为71.6%(0.49-99.29%)。aPCs中CD269的MFI-R(中位,范围)显著高于nPCs(4.13,1.12-26.88 vs 3.33,1.23-12.87),p < .0001。诊断时和复发时CD269的MFI中位(范围)分别为2.39(0.77-9.57)和2.66(2.15-3.23)。诊断时和复发时CD269水平相似,p = .5529。
Many novel therapies are being evaluated for the treatment of Multiple myeloma (MM). The cell-surface protein B-cell maturation antigen (BCMA, CD269) has recently emerged as a promising target for CAR-T cell and monoclonal-antibody therapies in MM. However, the knowledge of the BCMA expression-pattern in myeloma patients from the Indian subcontinent is still not available. We present an in-depth study of BCMA expression-pattern on abnormal plasma cells (aPC) in Indian MM patients.
We studied BM samples from 217 MM patients (211-new and 6-relapsed) with a median age of 56 years (range, 30-78 years & M:F-2.29) and 20 control samples. Expression levels/patterns of CD269 (clone-19f2) were evaluated in aPCs from MM patients and in normal PCs (nPC) from uninvolved staging bone marrow samples (controls) using multicolor flow cytometry (MFC). Expression-level of CD269 was determined as a ratio of mean fluorescent intensity (MFI-R) of CD269 in PCs to that of non-B-lymphocytes and expression-pattern (homogenous/heterogeneous) as coefficient-of-variation of immunofluorescence (CVIF).
Median (range) percentage of CD269-positive abnormal-PCs in total PCs was 71.6% (0.49-99.29%). The MFI-R (median, range) of CD269 was significantly higher in aPCs (4.13, 1.12-26.88) than nPCs (3.33, 1.23-12.87), p < .0001. Median (range) MFI of CD269 at diagnosis and relapse were 2.39 (0.77-9.57) and 2.66 (2.15-3.23) respectively. CD269 levels were similar at diagnosis and relapse, p = .5529.
We demonstrated that BCMA/CD269 is highly expressed in aPCs from a majority of MM patients, both at diagnosis and relapse. Thus, BCMA is a valuable target for therapy for Indian MM patients.
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