TY - JOUR
T1 - Charge-modified single chain antibody constructs of monoclonal antibody CC49
T2 - Generation, characterization, pharmacokinetics, and biodistribution analysis
AU - Pavlinkova, Gabriela
AU - Beresford, Guy
AU - Booth, Barbara J.M.
AU - Batra, Surinder K.
AU - Colcher, David
N1 - Funding Information:
These studies were supported by a grant from the United States Department of Energy (DE-FG02-95ER62024) and were conducted in the J. Bruce Henrikson Cancer Research Laboratories. We thank Heather Conway, Kay Devish, Jodi Halgren and Julia Westrich for their expert technical assistance and the Monoclonal Antibody Core Facility for their expertise. The CC49 scFv constructs were a generous gift from the National Cancer Institute Laboratory of Tumor Immunology (Dr. Jeffrey Schlom) and the Dow Chemical Company.
PY - 1999/1
Y1 - 1999/1
N2 - A novel strategy was developed in which an antibody scFv fragment of the monoclonal antibody (MAb) CC49 was modified by engineering DNA coding sequences to lower its isoelectric point. Negatively charged amino acids were added to the carboxy terminus of the CC49 V(H) region by adding nucleotide sequences in a polymerase chain reaction (PCR) amplification of the coding sequence of CC49 scFv. Two new DNA constructs coding for CC49 scFv with lower isoelectric points of 5.8 and 5.2 were engineered. These novel strategy- generated, charge-modified antibody constructs were compared for their immunological, pharmacokinetic, and biodistribution properties in athymic mice bearing LS-174T human colon carcinoma xenografts.
AB - A novel strategy was developed in which an antibody scFv fragment of the monoclonal antibody (MAb) CC49 was modified by engineering DNA coding sequences to lower its isoelectric point. Negatively charged amino acids were added to the carboxy terminus of the CC49 V(H) region by adding nucleotide sequences in a polymerase chain reaction (PCR) amplification of the coding sequence of CC49 scFv. Two new DNA constructs coding for CC49 scFv with lower isoelectric points of 5.8 and 5.2 were engineered. These novel strategy- generated, charge-modified antibody constructs were compared for their immunological, pharmacokinetic, and biodistribution properties in athymic mice bearing LS-174T human colon carcinoma xenografts.
KW - Antibody engineering
KW - Colon carcinoma xenografts
KW - Isoelectric point
KW - Radioimmunodiagnosis
KW - Single chain fragments
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U2 - 10.1016/S0969-8051(98)00075-4
DO - 10.1016/S0969-8051(98)00075-4
M3 - Article
C2 - 10096498
AN - SCOPUS:0032891911
SN - 0969-8051
VL - 26
SP - 27
EP - 34
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 1
ER -