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Biointron 2024-12-19

Recombinant antibody expression is a biotechnological process that involves engineering and producing antibodies outside their natural context using recombinant DNA technology. This method enables the development of antibodies with specific characteristics, such as different isotypes or formats, tailored for research, diagnostics, and therapeutic applications. Over the past two decades, recombinant antibodies have emerged as the fastest-growing class of therapeutic proteins.

Engineering Antibodies: From Formats to Production Systems

Customized Antibody Formats

Single-Chain Variable Fragments (scFv): Small, flexible antibodies used for therapeutic and diagnostic applications.
Fragment Antigen-Binding (Fab): Larger than scFv, these fragments include constant domains for improved stability.
Bispecific Antibodies: Molecules capable of targeting two different antigens simultaneously, with applications in cancer immunotherapy.
VHH Antibodies (Nanobodies): Single-domain antibodies derived from camelid species, known for their small size, stability, and ability to access challenging targets like enzyme active sites.
Antibody-Drug Conjugates (ADCs): Antibodies conjugated to cytotoxic drugs, allowing targeted delivery of therapeutics to specific cells, commonly used in oncology.

Other formats, such as diabodies and minibodies, extend the versatility of recombinant antibodies for specific needs.

Expression Systems for Recombinant Antibodies

A range of expression systems has been developed to produce recombinant antibodies efficiently, each with distinct advantages and limitations:

1. Prokaryotic Systems (e.g., E. coli):

Used for producing antibody fragments like scFv and Fab.
Advantages: High yields and cost-effectiveness.
Limitations: Lack of post-translational modifications (e.g., glycosylation).

2. Yeast and Fungi:

Combine eukaryotic processing capabilities with microbial robustness.
Glyco-engineered yeast strains can produce antibodies with human-like glycosylation.

3. Insect Cells:

Used for producing full-size antibodies with complex structures.
Can deliver high yields, but glycosylation differs from mammalian systems.

4. Mammalian Cells (e.g., CHO Cells):

The gold standard for therapeutic antibodies due to their ability to produce fully functional antibodies with human-like glycosylation.
Production titers have reached up to 27 g/L, with high product quality and reduced immunogenicity.

5. Transgenic Plants and Animals:

Emerging as scalable and cost-effective systems for large-scale production.
Challenges include differences in glycosylation patterns in plants and complex regulatory pathways for transgenic animals.

Recombinant antibody expression continues to revolutionize the production of therapeutic antibodies, offering unmatched flexibility and scalability. Advances in production systems, from optimized mammalian cell lines to emerging transgenic plants and animals, are reshaping the landscape of antibody manufacturing. With innovations in gene engineering, glyco-engineering, and transient production methods, recombinant antibodies are set to play an increasingly pivotal role in medicine, diagnostics, and research.