Ghetie V, Engert A, Schnell R, Vitetta E S
Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas 75235-8576, USA.
Cancer Lett. 1995 Nov 27;98(1):97-101.
We have compared the in vitro and in vivo activities of three deglycosylated ricin A chain (dgA)-containing immunotoxins (ITs) with one versus two molecules of dgA per molecule of IgG. Two of the ITs (anti-CD19-dgA2 and anti-CD25-dgA2) had 3-0-fold improvements over their dgA1 counterparts in vitro. However, the in vivo anti-tumor activity of both constructs of each IT was the same. In contrast, anti-CD22-dgA2 was 7-fold more potent in vitro and significantly more potent in vivo than its dgA1 counterpart. These studies suggest that monoclonal antibodies must be individually tested to determine whether the addition of two versus one dgA will improve cytotoxic activity in vivo.
我们比较了三种含去糖基化蓖麻毒素A链(dgA)的免疫毒素(ITs)的体外和体内活性,这些免疫毒素每分子IgG含有一分子或两分子dgA。其中两种ITs(抗CD19-dgA2和抗CD25-dgA2)在体外比其dgA1对应物有3至10倍的改善。然而,每种IT的两种构建体的体内抗肿瘤活性是相同的。相比之下,抗CD22-dgA2在体外的效力比其dgA1对应物高7倍,在体内的效力也显著更高。这些研究表明,必须对单克隆抗体进行单独测试,以确定添加两分子dgA与一分子dgA相比是否会提高体内细胞毒性活性。