Development of an ELISA to detect circulating anti-asparaginase antibodies in dogs with lymphoid neoplasia treated with Escherichia coli l-asparaginase

J. A. Kidd, P. Ross, A. S. Buntzman, P. R. Hess

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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. 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.

Original languageEnglish (US)
Pages (from-to)77-88
Number of pages12
JournalVeterinary and Comparative Oncology
Volume13
Issue number2
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

Keywords

  • Antibodies
  • Canine
  • ELISA
  • L-asparaginase
  • Lymphoma

ASJC Scopus subject areas

  • veterinary(all)

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