One step generation of fully chimeric antibodies using Cgamma1- and Ckappa mutant mice.
Humanized antibodies (Abs) are effective drugs against a variety of diseases such as cancer, autoimmune diseases, transplant rejection and others. The most powerful technology to develop humanized Abs is the use of mice that produce humanized Abs. By modifying the genetic background of F004 mice a new mouse substrain was developed for optimized "one step" generation of chimeric humanized monoclonal Abs. The new mice (F004-Jen) demonstrated improved fertility still expressing the human locus at the same level as the parental F004 mouse. The value of these mice for the generation of chimeric Abs was exemplified for a panel of chimeric Abs against the human neural cell adhesion molecule (NCAM): The fully chimeric human IgG1/kappa Ab Ch.MK1 bound to NCAM expressing cells with a K(D)=4.3-8.7 x 10(-8) M and was functionally active as demonstrated by depleting NCAM expressing cells. We also demonstrated that chimeric IgG1/kappa Abs can be induced by hybridoma class switching of IgM producing hybridoma cells, providing an alternative way to chimeric Abs. The present data highlight F004-Jen mice as an efficient tool for "one step" generation of chimeric Abs.
Jensen
Markus
M
Department of Pediatric Oncology, University of Cologne, Cologne, Germany. jensen@uni-koeln.de
Klehr
Martin
M
Vogel
Anna
A
Schmitz
Sandra
S
Tawadros
Samir
S
Mühlenhoff
Martina
M
Plück
Anne
A
Fischer
Thomas
T
Schomäcker
Klaus
K
Schultze
Joachim L
JL
Berthold
Frank
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D006825:Hybridomas; D017578:Immunoglobulin Class Switching; D007127:Immunoglobulin Constant Regions / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics / Q000276:immunology*; D050506:Mutant Chimeric Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019006:Neural Cell Adhesion Molecules / Q000032:analysis / Q000276:immunology*; D012098:Reproduction
D000911:Antibodies, Monoclonal; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D050506:Mutant Chimeric Proteins; D019006:Neural Cell Adhesion Molecules