Quantification of B-cell maturation antigen, a target for novel chimeric antigen receptor T-cell therapy in Myeloma.
Quantification of B-cell maturation antigen, a target for novel chimeric antigen receptor T-cell therapy in Myeloma.
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DOI：
10.1016/j.leukres.2018.07.015
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发表时间：
2018-08
影响因子：
2.7
通讯作者：
Stetler-Stevenson M
中科院分区：
文献类型：
--
作者：
Salem DA;Maric I;Yuan CM;Liewehr DJ;Venzon DJ;Kochenderfer J;Stetler-Stevenson M
B细胞成熟抗原(BCMA)由正常和恶性浆细胞表达，并通过抗BCMA嵌合抗原受体T细胞治疗(BCMA CAR T细胞治疗)靶向于浆细胞骨髓瘤(PCM)患者。表面BCMA的表达是CAR T细胞结合和杀伤所必需的。采用流式细胞术(FC)和免疫组织化学方法(IHC)检测BCMA在骨髓PCM细胞中的表达情况和强度。FC法检测70例患者PCM BCMA的表达，IHC法检测43例患者PCM BCMA的表达。BCMA在94%的患者中表达。FC可以评估所有标本中BCMA的表达，89%的病例表达是可量化的(QuantiBRITE System，BD Biosciences，San Jose，CA)。表达是高度可变的，可以从数字上分为暗淡、中等或明亮的表达水平。在43例同时进行免疫组化和免疫组化检测的标本中，免疫组化阳性率(97%)高于免疫组化(72.0%)，说明免疫组化比免疫组化更有价值(p=0.002，McNemar‘s检验)。我们认为，Fc比IHC更敏感，可用于客观定量骨髓瘤细胞BCMA的表达。当骨髓瘤有明显的骨髓浸润时，IHC主要有用，而对于骨髓瘤细胞数量较少的患者，IHC不太敏感。此外，Fc能够区分正常和异常的浆细胞，并对这些细胞上的BCMA进行定量，这使其成为筛选CAR T细胞治疗患者和后续治疗后的有用和敏感的工具。
B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells and is targeted via anti-BCMA chimeric antigen receptor T-cell therapy (BCMA CAR T-cell therapy) in plasma cell myeloma (PCM) patients. Surface BCMA expression is required for CAR T-cell binding and killing. We determined the incidence and intensity of expression of BCMA in bone marrow PCM cells using flow cytometry (FC) and immunohistochemistry (IHC). PCM BCMA expression was assessed by FC in 70 patients and in 43 concurrent specimens by IHC. BCMA expression was detected in 94% of patients. FC could assess BCMA expression in all specimens and expression was quantifiable (QuantiBRITE system, BD Biosciences, San Jose, CA) in 89% of cases. Expression was highly variable and could be numerically classified into dim, moderate or bright levels of expression. In the 43 specimens assessed successfully by both IHC and FC, FC showed higher positivity rate (97%) than IHC (72%), indicating that FC is more useful than IHC in detection of BCMA (p = 0.002; McNemar’s test). We conclude that FC is more sensitive than IHC and can be used to objectively quantify BCMA expression by myeloma cells. IHC is primarily useful when there is significant infiltration of the bone marrow by myeloma and is less sensitive with low numbers of myeloma cells. Furthermore, the ability of FC to differentiate between normal and abnormal plasma cells and to quantify BCMA on these cells, makes it a useful and sensitive tool in screening patients for CAR T-cell therapy and for follow-up post therapy.
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DOI：
10.1002/cyto.b.21249
发表时间：
2016-01
期刊：
Cytometry. Part B, Clinical cytometry
影响因子：
--
作者：
Stetler-Stevenson M;Paiva B;Stoolman L;Lin P;Jorgensen JL;Orfao A;Van Dongen J;Rawstron AC
通讯作者：
Rawstron AC
影响因子：
3.4
作者：
Wang, Lili;Abbasi, Fatima;Stetler-Stevenson, Maryalice
通讯作者：
Stetler-Stevenson, Maryalice
DOI：
10.3324/haematol.2009.009100
发表时间：
2009-11-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Paiva, Bruno;Vidriales, Maria-Belen;San Miguel, Jesus F.
通讯作者：
San Miguel, Jesus F.
影响因子：
3.4
作者：
Jasper, Gregory A.;Arun, Indu;Stetler-Stevenson, Maryalice
通讯作者：
Stetler-Stevenson, Maryalice
影响因子：
4.4
作者：
GRAS, MP;LAABI, Y;TSAPIS, A
通讯作者：
TSAPIS, A