Human Antibody Production Using Insect-Cell Expression Systems

Abstract

Insect-cell expression systems provide a reliable and effective means for generating biologically active human antibodies. Two methods are available for this purpose. Most notably, the baculovirus expression system is a wellestablished tool for rapidly producing functional immunoglobulins (Ig) and can generate antibody yields that rival or even surpass those achieved by other eukaryotic expression systems (1–5). Alternatively, a recently described transfection method allows the continuous expression of antibodies from stably transformed insect cells (6). Both methods offer an advantage over bacterial and yeast expression systems, as proteins generated in insect cells are correctly folded and processed (7). Although all of the authentic protein modifications (e.g., glycosylation) provided by mammalian expression systems are not evident for insect cell-expressed antibodies, these differences do not affect important Ig activities, including complement lysis activity and antibody-dependent cell-mediated cytotoxicity (8). When compared to mammalian-based systems, the methods required for generating and maintaining baculovirus recombinants and stable insect-cell transformants are simple and cost-effective, requiring incubation and storage without the support of carbon dioxide and liquid nitrogen, respectively. Furthermore, insect-cell expression systems provide a safer platform for producing therapeutic proteins because of the limited host range of baculoviruses and the absence of harmful factors (e.g., retroviral elements) potentially associated with mammalian cells.