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首页> 外文期刊>Veterinary and Comparative Oncology >Development of an ELISA to detect circulating anti-asparaginase antibodies in dogs with lymphoid neoplasia treated with Escherichia coli L-asparaginase
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Development of an ELISA to detect circulating anti-asparaginase antibodies in dogs with lymphoid neoplasia treated with Escherichia coli L-asparaginase

机译：ELISA的开发，以检测用大肠杆菌L-天冬酰胺酶治疗的淋巴瘤形成的犬中循环抗天冬酰胺酶抗体

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摘要

Resistance to Escherichia colil-asparaginase in canine lymphoma occurs frequently with repeated administration, a phenomenon often attributed, without substantiation, to the induction of neutralizing antibodies. To test the hypothesis that treated dogs develop antibodies against the drug, we created an enzyme-linked immunosorbent assay (ELISA) to measure plasma anti-asparaginase immunoglobulin G responses. Using samples from dogs that had received multiple doses, specific reactivity against l-asparaginase was demonstrated, while naive patients' samples were negative. The optimized ELISA appeared sensitive, with endpoint titers >1 600 000 in positive control dogs. Intra- and inter-assay coefficients of variation were 3.6 and 14.5%. The assay was supported by the observation that ELISA-positive plasma could immunoprecipitate asparaginase activity. When clinical patients were evaluated, 3/10 dogs developed titers after a single injection; with repeated administration, 4/7 dogs were positive. l-asparaginase antibodies showed reduced binding to the PEGylated drug formulation. The ELISA should prove useful in investigating the potential correlation of antibody responses with resistance.
机译：反复给药经常导致犬淋巴瘤中对大肠杆菌-天冬酰胺酶的抗药性，这种现象通常归因于中和抗体的诱导，而没有证实。为了测试假犬对药物产生抗体的假说，我们创建了一种酶联免疫吸附测定（ELISA）来测量血浆抗天冬酰胺酶免疫球蛋白G的反应。使用来自接受多次剂量的狗的样品，证明了针对l-天冬酰胺酶的特异性反应性，而未接受过治疗的患者样品为阴性。优化的ELISA表现出敏感性，阳性对照犬的终点滴度> 1 600 000。批内和批间变异系数分别为3.6和14.5％。 ELISA阳性血浆可免疫沉淀天冬酰胺酶活性的观察结果支持了该测定。对临床患者进行评估时，单次注射后有3/10只狗出现了滴度。重复给药后，有4/7只狗呈阳性。 1-天冬酰胺酶抗体显示出与PEG化药物制剂的结合减少。 ELISA应该证明对研究抗体反应与耐药性之间的潜在相关性很有用。

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