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ELISA against circulating anti-asparaginase antibodies in dogs with lymphoid neoplasia
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Lymphomas belong to the most common malignant tumours in dogs and they are in most cases very sensitive to chemotherapy. L-aspariginase is one of the commonly used chemotherapeutic substances, but unfortunately resistance to Escherichia coli l-asparaginase in canine lymphoma occurs frequently with repeated administration, a phenomenon often attributed, without substantiation, to the induction of neutralizing antibodies.
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The objective of this study was 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 naïve 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.
Source: Kidd, J. A., Ross, P., Buntzman, A. S. and
Hess, P. R. (2015), Development of an ELISA to detect circulating anti-asparaginase antibodies in dogs with lymphoid neoplasia treated with Escherichia coli l-asparaginase. Veterinary and Comparative Oncology, 13: 77–88. doi: 10.1111/vco.12014
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