Conry R M, Bantia S, Turner H S, Barlow D L, Allen K O, LoBuglio A F, Montgomery J A, Walsh G M
Comprehensive Cancer Center, The University of Alabama at Birmingham, 35294-3300, USA.
Immunopharmacology. 1998 Jul;40(1):1-9. doi: 10.1016/s0162-3109(98)00012-5.
The antiproliferative effect of BCX-34 was tested in normal human peripheral blood mononuclear cells (PBMCs) induced to proliferate with OKT3, tetanus toxoid, the mixed lymphocyte reaction, or IL-2. In the case of OKT3, tetanus toxoid, or the MLR the IC50s ranged between 0.7 and 4 microM. With IL-2, the IC50 was 14.6 microM. In T-cells purified by rosetting the IC50 with IL-2 was 0.62 microM. In CD4 or CD8 cells obtained by magnetic activated cell sorting the IC50s with IL-2 were 0.24 and 0.62 microM, respectively. BCX-34 inhibition of proliferation in human PBMCs may not depend entirely upon the accumulation of intracellular dGTP because tetanus toxoid-induced proliferation was inhibited in the absence of deoxyguanosine and was not reversed by deoxycytidine. BCX-34 did not inhibit IL-2 release from PBMCs and did not alter PBMC viability. The results of these studies show that BCX-34 is a potent inhibitor of normal human T-cell proliferation induced by antigenic or IL-2 stimulation. BCX-34 in normal human T-cells has a deoxyguanosine-independent mechanism to suppress in vitro proliferation. BCX-34 appears to have little effect on T-cell viability. The data suggest that BCX-34 may be useful in the treatment of T-cell proliferative disorders.
在经OKT3、破伤风类毒素、混合淋巴细胞反应或白细胞介素-2诱导增殖的正常人外周血单个核细胞（PBMC）中测试了BCX-34的抗增殖作用。在OKT3、破伤风类毒素或混合淋巴细胞反应的情况下，半数抑制浓度（IC50）在0.7至4微摩尔之间。对于白细胞介素-2，IC50为14.6微摩尔。在用玫瑰花结法纯化的T细胞中，与白细胞介素-2的IC50为0.62微摩尔。在通过磁珠激活细胞分选获得的CD4或CD8细胞中，与白细胞介素-2的IC50分别为0.24和0.62微摩尔。BCX-34对人PBMC增殖的抑制作用可能并不完全取决于细胞内脱氧鸟苷三磷酸（dGTP）的积累，因为在没有脱氧鸟苷的情况下破伤风类毒素诱导的增殖受到抑制，且脱氧胞苷不能逆转这种抑制作用。BCX-34不抑制PBMC释放白细胞介素-2，也不改变PBMC的活力。这些研究结果表明，BCX-34是抗原或白细胞介素-2刺激诱导的正常人T细胞增殖的有效抑制剂。在正常人T细胞中，BCX-34具有一种不依赖脱氧鸟苷的机制来抑制体外增殖。BCX-34似乎对T细胞活力影响很小。数据表明，BCX-34可能对治疗T细胞增殖性疾病有用。
