PMID- 7105004
OWN - NLM
STAT- MEDLINE
DCOM- 19821029
LR  - 20071114
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 42
IP  - 10
DP  - 1982 Oct
TI  - Immunological and pharmacological characterization of poly-DL-alanyl-modified 
      Erwinia carotovora L-asparaginase.
PG  - 4068-71
AB  - The covalent attachment of poly-DL-alanine peptides to lysyl residues on the 
      surface of Erwinia carotovora L-asparaginase has produced a modified enzyme which 
      is much less immunogenic in mice and demonstrates 100-fold longer plasma 
      half-life in the rhesus monkey. Immunogenic responses towards both the 
      immunoglobulin G (IgG) and immunoglobulin E (IgE) antibody subclasses were 
      evaluated in C57BL x DBA/2 F1 mice exposed to 250 rads of whole-body irradiation 
      4 hr prior to immunization with 5-diazo-4-oxynorvaline-inactivated native and 
      modified L-asparaginase in complete Freund's adjuvant. Under these 
      immunologically stressful conditions, the native enzyme evoked an IgE and IgG 
      response which could be further amplified by a secondary immunization, whereas 
      the modified enzyme evoked no IgE or IgG response even after a tertiary 
      immunization. In experiments mimicking an intensive therapeutic schedule, whereby 
      two groups of mice were given weekly injections of 5 to 10 units of either native 
      or modified asparaginase for up to 14 weeks, neither enzyme form evoked a 
      significant IgE response, and only the mice given injections of the native enzyme 
      produced an IgG response. In a preliminary patient study, skin testing of a child 
      who had shown an allergic reaction to the native enzyme resulted in a negative 
      response after an intradermal injection of the modified enzyme, whereas a wheal 
      and flare reaction was observed to both the native enzyme and a histamine 
      control. All of these results suggest that the modified enzyme should show a 
      definite reduction in immunological reactions associated with L-asparaginase 
      treatment of childhood leukemia.
FAU - Uren, J R
AU  - Uren JR
FAU - Hargis, B J
AU  - Hargis BJ
FAU - Beardsley, P
AU  - Beardsley P
LA  - eng
GR  - CA 26358/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Allergens)
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Peptides)
RN  - 25191-17-7 (polyalanine)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 3.5.1.1 (Asparaginase)
SB  - IM
MH  - Allergens
MH  - Animals
MH  - Antigen-Antibody Complex
MH  - Asparaginase/blood/*immunology/toxicity
MH  - Erwinia/*enzymology
MH  - Humans
MH  - Immunoglobulin E
MH  - Immunoglobulin G
MH  - Kinetics
MH  - Macaca mulatta
MH  - Mice
MH  - Peptides/*pharmacology
MH  - Skin Tests
EDAT- 1982/10/01 00:00
MHDA- 1982/10/01 00:01
CRDT- 1982/10/01 00:00
PHST- 1982/10/01 00:00 [pubmed]
PHST- 1982/10/01 00:01 [medline]
PHST- 1982/10/01 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1982 Oct;42(10):4068-71.