Studies on neutralization of L-asparaginase activity in vitro and in vivo

✍ Scribed by Srikrishna Vadlamudi; Martin Padarathsingh; Enzo Bonmassar; Vaman Waravdekar; Abraham Goldin

• Publisher: John Wiley and Sons
• Year: 1971
• Tongue: English
• Weight: 545 KB
• Volume: 27
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/1097-0142(197106)27:6<1321::aid-cncr2820270607>3.0.co;2-y

✦ Synopsis

L-asparaginase was effective in increasing the life span of leukemic (L5178Y) mice. However, the therapeutic effect of the drug was reduced when this treatment was preceded by a series of pretreatments (relative to tumor implantation) with the drug. T h e data from in vitro and in vivo studies revealed the involvement of humoral antibodies to L-asparaginase in reducing therapeutic activity of the d r u g in leukemic mice. Similarly, the antileukemic activity of the drug was neutralized when L-asparaginase was pre-incubated with immune sera obtained from rabbits or mice. The therapeutic activity of the drug was retained when the pretreatment with L-asparaginase in mice was accompanied by a single injection of cyclophosphamide, an immunosuppressant drug. Sera from these mice did not contain precipitin antibody to L-asparaginase.

OLLOWING THE INITIAL OBSERVATION BY

F Kidds that normal guinea pig sera have antitumor activity, further investigations by Broome2 led to the identification of the active principal in the sera as L-asparaginase (A-ase). Isolation and purification of this enzyme from bacterial source (Escherirhia coli) was then achieved by Mashburn and Wris-T h e therapeutic effectiveness of A-ase derived from E. coli has been demonstrated in 6CSHED lymphoma, EARAD,, L5178Y leukemia in mice, primary lymphosarcoma in dogs, and acute lymphoblastic leukemia in children.lJ0811 T h e results of experiments dealing with A-ase (E. coli) toxicity in monkeys and allergenicity in guinea pigs have Prcscnted, in part, at the