181. For monoclonal antibody production, mammalian expression systems are preferred over
bacterial expression systems, primarily because:
A. mammalian cultures have better productivity
B. mammalian cultures produce extra-cellular product simplifying the purification steps
C. mammalian system provide necessary post-translational modifications
D. mammalian genes can only be expressed in mammalian systems

Overview

Monoclonal antibodies (mAbs) are complex glycoproteins widely used in therapeutics and diagnostics. Producing them in systems that accurately mimic human cell biology is essential for function, safety, and efficacy.

Why Bacterial Systems Fall Short

• Lack of Post-Translational Modifications (PTMs):
  Bacteria like E. coli do not glycosylate proteins or carry out complex folding and disulfide bond formation as required by many functional mAbs.

• Inclusion Body Formation:
  Antibodies often misfold and form inclusion bodies in bacterial hosts, necessitating complex refolding steps.

• Improper Folding and Stability:
  Bacterial cytoplasm lacks the machinery for forming correct antibody structures (especially disulfide bonds in the heavy and light chains).

Why Mammalian Systems Excel

• Correct Post-Translational Modifications:
  Mammalian cells like CHO (Chinese Hamster Ovary) and HEK293 lines can:

  • Glycosylate proteins

  • Form proper disulfide bonds

  • Enable protein folding and secretion similar to human physiology

• Biological Activity and Stability:
  These modifications ensure that antibodies are biologically active, stable, and less immunogenic in humans.

• Secretion into Medium:
  Antibodies are secreted into the culture medium, simplifying downstream purification.

Conclusion

The primary reason for choosing mammalian expression systems for monoclonal antibody production is their ability to perform necessary post-translational modifications that are crucial for the structure and function of therapeutic antibodies.

Correct Answer: C. Mammalian system provide necessary post-translational modifications