Monoclonal antibodies can protect L-asparaginase against inactivation by trypsin.
We show that a non-inhibitory monoclonal antibody (MAB) can be selected that provides substantial and sustained protection against proteolytic inactivation of L-asparaginase by trypsin. Of six non-inhibitory, high affinity, monoclonal antibodies to L-asparaginase, one afforded approximately 70% protection. Inactivation of L-asparaginase is associated with a single cleavage adjacent to lysine-29 that results in loss of an N-terminal fragment with a calculated MW of 2,647. The protective MAB prevented this trypsin cleavage. The products of gene fusions of "humanized" fragments of such antibodies and L-asparaginase could have increased clinical utility.
Hybrisens Ltd., Toronto, Ontario, Canada.
M
M
Ramjeesingh
M
M
Zywulko
A
A
Rothstein
E Y
EY
Shami
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001215:Asparaginase / Q000276:immunology*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D015151:Immunoblotting; D014357:Trypsin
D000911:Antibodies, Monoclonal; D014357:Trypsin; D001215:Asparaginase