Productivity and quality of recombinant proteins produced by stable CHO cell clones can be predicted by transient expression in HEK cells.
Selection of lead candidates in drug discovery is a complex and time-consuming process. Here, we describe an approach that allows prediction of the productivity and quality of recombinant proteins by stable producer cell clones with the help of transient transfection studies. This is exemplified for three distinct bispecific T cell engager (BiTE(®))-a new class of single-chain antibody-based therapeutics showing very promising results in the treatment of cancer. BiTE(®) titers of transiently transfected HEK cells showed a striking correlation with titers of selected stable CHO cell clones. Likewise, the percentage of the monomeric BiTE(®) fraction in cell culture supernatants correlated well between transiently expressing HEK and stably expressing CHO cell clones. This validates the use of transient transfection studies for the selection of biopharmaceutical lead candidates with desired pharmaceutical properties.
Amgen Research, Munich, Germany.
Carolin
C
Diepenbruck
Matthias
M
Klinger
Thomas
T
Urbig
Patrick
P
Baeuerle
Rüdiger
R
Neef
D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D018929:Cell Culture Techniques; D002999:Clone Cells / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014162:Transfection / Q000379:methods*
D000906:Antibodies; D011994:Recombinant Proteins