title: One step generation of fully chimeric antibodies using Cgamma1- and Ckappa mutant mice.
abstract: 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.
authors.affiliation: Department of Pediatric Oncology, University of Cologne, Cologne, Germany. jensen@uni-koeln.de
authors.forename: Markus
authors.initials: M
authors.lastname: Jensen
authors.forename: Martin
authors.initials: M
authors.lastname: Klehr
authors.forename: Anna
authors.initials: A
authors.lastname: Vogel
authors.forename: Sandra
authors.initials: S
authors.lastname: Schmitz
authors.forename: Samir
authors.initials: S
authors.lastname: Tawadros
authors.forename: Martina
authors.initials: M
authors.lastname: Mühlenhoff
authors.forename: Anne
authors.initials: A
authors.lastname: Plück
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischer
authors.forename: Klaus
authors.initials: K
authors.lastname: Schomäcker
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
authors.forename: Frank
authors.initials: F
authors.lastname: Berthold
mesh_terms: 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
chemical_list: 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