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Asparaginase (E. coli)

Also known as Elspar, Spectrila, L-asparaginase

An enzyme from Escherichia coli that removes the amino acid asparagine from the blood. It is given by injection as part of multi-agent treatment of acute lymphoblastic leukaemia.

From discovery to approval

  1. 1953 · First described

    In 1953 Kidd reported that repeated injections of normal guinea pig serum made two kinds of transplanted lymphoma regress in mice, and that the active material appeared to be a protein. In 1961 and 1963 Broome reported evidence that the serum's L-asparaginase accounted for the effect.[2][3][4][5][6][7][8][9][10]

  2. 1978-01-10 · FDA regular · 25 years after first description

    As a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL)[11]

  3. 2016-01-14 · EMA regular · 63 years after first description

    Marketing authorisation issued 14 January 2016 (EPAR page); as a component of antineoplastic combination therapy for acute lymphoblastic leukaemia in paediatric patients from birth to 18 years and in adults. No conditional, exceptional or accelerated wording was found, so 'regular' is an inference.[12]

How it works

Depletes asparagine in the blood. The label says some leukaemic cells cannot make asparagine because they lack asparagine synthetase, so they depend on outside supply and are thought to die when it is removed; normal cells, which can make it, are less affected.[1]

Where it came from and why

No source read says why Kidd tried guinea pig serum; a 2014 history calls the result surprising. Broome then tested whether the serum's L-asparaginase explained it: antilymphoma activity was found only in serum fractions containing the enzyme, and lymphoma cells grown without asparagine lost their susceptibility to the serum.

In 1953 J. G. Kidd reported that repeated injections of normal guinea pig serum made two kinds of transplanted lymphoma regress in mice, while horse or rabbit serum did not have this effect [2]. In a companion paper he found that the active material precipitated with ammonium sulfate and was destroyed by chymotrypsin, suggesting a protein whose identity he could not establish [3]. A 2014 history calls the finding surprising [8].

In 1961 J. D. Broome published a short report whose title says the L-asparaginase activity of guinea pig serum is responsible for its antilymphoma effects [4]. His 1963 papers reported that the serum enzyme's properties were indistinguishable from those of the antilymphoma agent, that activity was found only in fractions containing the enzyme [5], and that lymphoma cells cultured without asparagine lost their susceptibility to the serum [6]. The same history credits Bertha Madras with the hypothesis that cells with low asparagine synthetase are the ones killed [8].

A 1964 paper's title reports a tumour-inhibitory effect of L-asparaginase from Escherichia coli [7], and the title of a 1967 JAMA paper speaks of remission in human leukaemia [9]. The FDA lists the E. coli product Elspar with an approval date of 10 January 1978 [10].

Cancers

  • Acute lymphoblastic leukaemia

    The 2013 US label for Elspar lists use as a component of a multi-agent regimen for acute lymphoblastic leukaemia.[1]

  • Acute lymphoblastic leukaemia (EU authorisation)

    The EU authorisation of Spectrila, an asparaginase produced in E. coli by recombinant DNA technology (product information), covers use as a component of antineoplastic combination therapy in paediatric patients from birth to 18 years and in adults.[12]

  • Lymphoma (transplanted mouse lymphomas)

    Kidd's 1953 experiments, in which guinea pig serum made two kinds of transplanted lymphoma regress in mice.[2]

Family and partners

Drugs derived from it: Pegaspargase

Worth knowing

  • In Kidd's 1953 experiments, transplanted lymphomas regressed after guinea pig serum, but two transplanted mammary carcinomas and a fibrosarcoma grew unimpeded in similarly treated hosts.[2]
  • A 2023 review notes that the native E. coli enzyme was authorised by the FDA in 1978 but is currently no longer available in the United States for use in children under 18 years of age.[13]
  • A 2011 review states that hypersensitivity reactions and silent inactivation due to antibodies against E. coli asparaginase lead to inactivation of the enzyme in up to 60% of cases.[14]
  • A 2006 review states that modern treatment of childhood acute lymphoblastic leukaemia uses enzyme-based depletion of blood asparagine, and that drug-resistant disease may correlate with up-regulation of asparagine synthetase.[15]

On this site

References

  1. U.S. Food and Drug Administration. Elspar (asparaginase) prescribing information, BLA 101063, supplement 5169 approved 16 July 2013 (the label states it may not be the latest approved). Source
  2. KIDD JG. Regression of transplanted lymphomas induced in vivo by means of normal guinea pig serum. I. Course of transplanted cancers of various kinds in mice and rats given guinea pig serum, horse serum, or rabbit serum. J Exp Med. 1953;98(6):565-82. PubMedDOI
  3. KIDD JG. Regression of transplanted lymphomas induced in vivo by means of normal guinea pig serum. II. Studies on the nature of the active serum constituent: histological mechanism of the regression: tests for effects of guinea pig serum on lymphoma cells in vitro: discussion. J Exp Med. 1953;98(6):583-606. PubMedDOI
  4. Broome JD. Evidence that the L-asparaginase activity of guinea pig serum is responsible for its antilymphoma effects. Nature. 1961;191(4793):1114-5. DOI
  5. BROOME JD. Evidence that the L-asparaginase of guinea pig serum is responsible for its antilymphoma effects. I. Properties of the L-asparaginase of guinea pig serum in relation to those of the antilymphoma substance. J Exp Med. 1963;118(1):99-120. PubMedDOI
  6. BROOME JD. Evidence that the L-asparaginase of guinea pig serum is responsible for its antilymphoma effects. II. Lymphoma 6C3HED cells cultured in a medium devoid of L-asparagine lose their susceptibility to the effects of guinea pig serum in vivo. J Exp Med. 1963;118(1):121-48. PubMedDOI
  7. MASHBURN LT, WRISTON JC Jr. TUMOR INHIBITORY EFFECT OF L-ASPARAGINASE FROM ESCHERICHIA COLI. Arch Biochem Biophys. 1964;105:450-2. PubMedDOI
  8. Seeman P. Discovery of why acute lymphoblastic leukaemia cells are killed by asparaginase: Adventures of a young post-doctoral student, Bertha K Madras. J Med Biogr. 2014;22(2):90-2. PubMedDOI
  9. Hill JM, Roberts J, Loeb E, Khan A, MacLellan A, Hill RW. L-asparaginase therapy for leukemia and other malignant neoplasms. Remission in human leukemia. JAMA. 1967;202(9):882-8. PubMedDOI
  10. U.S. Food and Drug Administration. Drugs@FDA: approval date(s) and history, letters, labels for BLA 101063 (Elspar, asparaginase). Page read 2026-10-29. Source
  11. U.S. Food and Drug Administration, Oncology Center of Excellence. Pediatric Oncology Drug Approvals (table current as of February 2026; page content current as of 03/03/2026). Accessed 2026-10-20. Source
  12. European Medicines Agency. Spectrila (asparaginase): European public assessment report (EPAR) page and product information; marketing authorisation issued 14 January 2016. The product information states that it is produced in Escherichia coli cells by recombinant DNA technology. Pages read 2026-10-29. Source
  13. Tong WH, Rizzari C. Back to the future: the amazing journey of the therapeutic anti-leukemia enzyme asparaginase Erwinia chrysanthemi. Haematologica. 2023;108(10):2606-2615. PubMedDOI
  14. Pieters R, Hunger SP, Boos J, Rizzari C, Silverman L, Baruchel A, et al. L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase. Cancer. 2011;117(2):238-49. PubMedDOI
  15. Richards NG, Kilberg MS. Asparagine synthetase chemotherapy. Annu Rev Biochem. 2006;75:629-54. PubMedDOI
  16. Oettgen HF, Old LJ, Boyse EA, Campbell HA, Philips FS, Clarkson BD, et al. Inhibition of leukemias in man by L-asparaginase. Cancer Res. 1967;27(12):2619-31. PubMed
  17. Dolowy WC, Henson D, Cornet J, Sellin H. Toxic and antineoplastic effects of L-asparaginase. Study of mice with lymphoma and normal monkeys and report on a child with leukemia. Cancer. 1966;19(12):1813-9. PubMedDOI