Lohse Louise, Nielsen Jens, Kamstrup Søren, Oleksiewicz Martin B, Eriksen Lis
Danish Institute for Food and Veterinary Research, Department of Virology, Lindholm, Kalvehave, Denmark.
APMIS. 2005 Jul-Aug;113(7-8):489-96. doi: 10.1111/j.1600-0463.2005.apm_62.x.
In humans and cattle, multiple injections of murine monoclonal antibodies (m-mAbs) induce anti-mouse antibody responses. The objectives of the present study were to investigate whether a similar response could be seen when pigs were subjected to m-mAb therapy, and to study the kinetics of such a response. In two separate animal experiments, long-term treatment was performed with m-mAbs at low-dose levels and therapeutic levels, respectively. Two specific m-mAbs that recognized cognate antigen in the pigs (CD4 and CD8 surface antigens on T-lymphocytes) and two irrelevant control m-mAbs having no cognate antigen in the pigs were used. Enzyme-linked immunosorbent assays (ELISA) were used to quantitate the circulating m-mAbs, as well as the induced pig anti-mouse antibodies (PAMA), in serum samples from m-mAb-treated pigs. As expected, we generally saw vigorous PAMA responses within 10 days after the start of m-mAb treatment with the specific m-mAbs. However, the different mAbs showed striking differences in the kinetics and levels of PAMA responses, differences that might be ascribed to the m-mAb formulation and epitope specificity. In conclusion, treatment of pigs with m-mAbs against T-cell surface antigens induced rapid PAMA responses. This may influence and possibly decrease the effect of the m-mAb treatment by narrowing the time period where m-mAbs can efficiently be used for cell depletion.
在人类和牛中，多次注射鼠单克隆抗体（m - mAbs）会诱导抗小鼠抗体反应。本研究的目的是调查猪接受m - mAb治疗时是否会出现类似反应，并研究这种反应的动力学。在两个独立的动物实验中，分别以低剂量水平和治疗水平用m - mAbs进行长期治疗。使用了两种能识别猪体内同源抗原（T淋巴细胞上的CD4和CD8表面抗原）的特异性m - mAbs，以及两种在猪体内没有同源抗原的无关对照m - mAbs。酶联免疫吸附测定（ELISA）用于定量m - mAb治疗猪的血清样本中循环的m - mAbs以及诱导产生的猪抗小鼠抗体（PAMA）。正如预期的那样，在用特异性m - mAbs开始治疗后的10天内，我们通常看到强烈的PAMA反应。然而，不同的mAb在PAMA反应的动力学和水平上表现出显著差异，这些差异可能归因于m - mAb的制剂和表位特异性。总之，用针对T细胞表面抗原的m - mAbs治疗猪会诱导快速的PAMA反应。这可能会影响并可能降低m - mAb治疗的效果，因为它缩短了m - mAbs可有效用于细胞清除的时间段。
