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Note: TNF, tumor necrosis factor; IFN, interferon; VCAM, vascular cell adhesion molecule. aAll research applications

Note: TNF, tumor necrosis factor; IFN, interferon; VCAM, vascular cell adhesion molecule. aAll research applications various other cell types are used as substrate for the production of biologicals.

On the one hand, this might be of historical reason. Certain cell lines are well established; the production of vaccines and systems for manufacture have been optimized already. On the other hand, cell lines synthesizing proteins naturally without transformation procedures have clear advantages considering the production process (where a selective pressure to maintain expression is hence not necessary) and acceptance of the final product. Other cell lines have been shown to possess valuable properties such as glycosylation characteristics. This section describes some of these cell lines and their biotechnological usage; although not great in number, they are still significant in the pharmaceutical industry.

VERO cells, derived from the kidney of a normal adult African green monkey, are susceptible to a wide range of viruses, including measles, polioviruses, and rubella. These properties led to the early establishment of vaccine production in VERO cells (for polio) (Table 6). This now rather classical cell line is still used as capable substrate for virus production. VERO cells replaced primary monkey kidney cells for the production of oral polio vaccine and are now cultured on microcarriers in large-scale bioreactors (68). They were also successfully applied for the study of infection with Aujeszky virus in the VERAX system, a perfused fluidized bed with macroporous collagen carriers as microspheres to evaluate the possibility of vaccine production in a high-cell-density system (67). Baijot et al. (65)

established the manufacture of an Aujeszky vaccine using swine testicular cells (NLST) on microcarriers. Although VERO cells are mostly grown as attached cells, they can be adapted to grow in suspension in serum-free medium (70). The inducible expression of HIV-1 viruslike particles in transfected VERO and COS 7 cells (a SV 40 transformed monkey kidney cell line) was described by Haynes et al. (69). This important development offers an exciting alternative to the use of live virus vectors for the production and evaluation of AIDS vaccines based on noninfectious particles.

The human lymphoblastoid cell line Namalwa has been used as substrate for biologicals since the 1970s. The secretion of INF-a being naturally induced in Namalwa cells by treatment with sodium butyrate and addition of sendai virus is well established for industrial manufacturing (61). Process optimization and increase of productivity are still continuing and achieved by various modifications, such as treatment with tetramethyl urea (62) or sequential induction with sendai virus (63). Namalwa KJM 1 was derived from Namalwa and adapted to grow in serum-free medium. Miyaji et al. (71) describe the efficient expression of recombinant human INF-/ in these cells in high-cell-density perfusion culture. The comparison of recombinant pro-urokinase expression in Namalwa KJM 1 and CHO cells revealed a partly cleaved and thereby inactive form secreted in CHO cells due to proteases present in the supernatant (64). Because the protein secreted by Namalwa KJM 1 showed a single-chain form, this indicates that

Table 6. Examples of Cell lines and Their Use in Biotechnological Processes

Cell Line

Product

Application®

Ref.

293 (human embryonal kidney, Ad5 transformed)

Acetylcholinesterase

Structural and functional analysis (RA)

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