VEGF及其受体在恶性血液细胞系HL-60及Raji的表达

为了探讨血管内皮生长因子 (VEGF)在恶性血液病中的作用 ,以恶性血液细胞系HL 6 0和Raji为实验对象 ,应用RT PCR及ELISA法检测肿瘤细胞。VEGF基因的表达 ,并采用免疫组织化学染色法测定细胞表面VEGF受体Flt 1的表达。结果显示 :髓性白血病细胞系HL 6 0和淋巴瘤细胞系Raji中均存在VEGF mRNA的表达。在培养 4 8小时后 ,HL 6 0细胞和Raji细胞的培养上清液中VEGF含量明显高于正常人外周血单个核细胞。VEGF R(Flt 1)在两种肿瘤细胞的胞膜上均有表达 ,而正常人外周血单个核细胞上无表达。这一结果表明 ,白血病和淋巴瘤细胞具有产生VEGF的能力 ,并可将VEGF分泌到细胞外基质微环境中。VEGF可作用于白血病和淋巴瘤细胞本身 ,在恶性血液肿瘤细胞中存有VEGF的自分泌途径 ,而VEGF的自分泌成为血液肿瘤细胞高侵袭性生物学特性的基础。结论 :抑制VEGF的分泌将有助于阻断其与内皮细胞间的互动环 ,降低其增殖、抗凋亡和侵袭性能 。

4-1BBL分子在人恶性血液病细胞系的表达

目的:研究共刺激分子4-1BBL分子在人恶性血液病细胞系的表达及其生物学意义。方法:流式细胞仪检测4-1BBL分子在不同的人恶性血液病细胞系的表达;用可介导4-1BBL逆向信号的鼠抗人4-1BBL单抗(mAb1F1)作用于8个不同的人恶性血液病细胞系,细胞计数法和3H-TdR掺入法评价细胞系的体外生长和增殖。结果:FACS结果显示4-1BBL分子在人恶性血液病细胞系上有不同程度的表达,其中髓性白血病细胞系U937、HL60及B淋巴瘤细胞系Raji、Daudi上呈现较高水平的表达。细胞计数和3H-TdR掺入实验结果表明mAb1F1对髓性白血病细胞系U937和HL60,具有较强的促增殖效应。结论:共刺激分子4-1BBL分子在髓性白血病细胞系和B淋巴瘤细胞系上表达率较高;4-1BBL分子可通过介导逆向信号促进髓性白血病细胞系U937和HL60的生长和增殖。

Adoptive therapy with CAR redirected T cells for hematological malignancies

The survival of patients with hematological malignancies has been significantly improved due to the development of new therapeutic agents. However, relapse remains a major matter for concern. Recently, T cells engineered with chimeric antigen receptor(CAR) were reported to show unprecedented responses in a range of hematological malignancies. The persistence of the CAR-T cell can last for years and tends toward long-term antitumor memory by which relapses can be effectively prevented. The primary side effects that appear in most clinical trials are cytokine release syndrome and neurotoxicity. However, these symptoms can be treated and reversed. In this review, we describe CAR structure and function and summarize recent advances in CAR-T cell therapy in hematological malignancies.