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Recombinant monoclonal antibody

Introduction

Recombinant monoclonal antibodies (mAbs) are laboratory-engineered antibodies produced using recombinant DNA technology. These antibodies are highly specific to a particular antigen and are widely used in therapeutic, diagnostic, and research applications. Compared to traditional monoclonal antibodies generated via hybridoma technology, recombinant mAbs offer enhanced flexibility in design, higher reproducibility, and reduced immunogenicity.

Production of Recombinant Monoclonal Antibodies

  • Gene Cloning and Sequence Design: The variable regions (V_H and V_L) of the antibody are identified and cloned from immunized animals, hybridomas, or phage display libraries. Genes are fused with sequences encoding constant regions (e.g., human IgG1, IgG4) for therapeutic use.
  • Expression Vectors: Optimized plasmids containing the antibody genes, strong promoters (e.g., CMV), and selection markers (e.g., antibiotic resistance) are constructed for transfection into host cells.
  • Expression Systems:
    • Mammalian Cells: Chinese Hamster Ovary (CHO) cells are the gold standard, ensuring proper folding, glycosylation, and post-translational modifications.
    • Alternative Hosts: HEK293 cells, insect cells, and yeast systems are also used based on the required product properties.
  • Protein Expression and Purification: Transfected cells produce antibodies, which are secreted into the culture medium. Purification involves protein A/G affinity chromatography, followed by size-exclusion or ion-exchange chromatography for enhanced purity.
  • Quality Control: Rigorous testing ensures product consistency, binding affinity, glycosylation patterns, and structural integrity.

Advantages of Recombinant Monoclonal Antibodies

  • Flexibility in Engineering: Allows for humanization, affinity maturation, or Fc region modification to tailor antibodies for specific applications. Enables the development of bispecific antibodies, antibody-drug conjugates (ADCs), and fragments (Fab, scFv).
  • Reduced Immunogenicity: Fully human or humanized recombinant mAbs minimize immune responses in therapeutic applications.
  • Scalability and Reproducibility: Recombinant production systems offer consistent yield and quality, essential for clinical and industrial use.
  • Advanced Functional Modifications: Fc engineering to enhance effector functions (e.g., ADCC, CDC) or extend half-life via interaction with FcRn.

Applications of Recombinant Monoclonal Antibodies

  • Therapeutics:
    • Cancer: Targeting tumor antigens like HER2 (Trastuzumab) or immune checkpoints like PD-1/PD-L1 (Pembrolizumab, Nivolumab).
    • Autoimmune Diseases: Neutralizing inflammatory mediators (e.g., TNF-α inhibitors like Adalimumab).
    • Infectious Diseases: Neutralizing antibodies against SARS-CoV-2 and other pathogens.
    • Rare Diseases: Target-specific mAbs for niche conditions such as enzyme replacement therapies.
  • Diagnostics: Used in ELISA, immunohistochemistry, and flow cytometry for detecting disease biomarkers or antigens. Radiolabeled mAbs enable imaging for cancer diagnostics.
  • Research Tools: Recombinant mAbs are standard reagents for protein-protein interaction studies, pathway elucidation, and high-throughput screening.
  • Vaccine Development: Recombinant mAbs are utilized to study immune responses and validate vaccine efficacy.
  • Biosensors: Coupling recombinant mAbs with detection systems creates highly specific and sensitive diagnostic tools.

Challenges in Recombinant Monoclonal Antibody Development

  • Complexity of Production: Requires advanced expression systems and optimization to ensure proper folding and glycosylation. Production costs remain high, particularly for large-scale manufacturing.
  • Immunogenicity Risk: Despite humanization, some antibodies may still elicit immune responses in patients.
  • Target Escape Mechanisms: Resistance due to target mutation (e.g., in cancer) can reduce efficacy over time.
  • Regulatory Hurdles: Stringent testing and validation are required to ensure safety and efficacy, prolonging development timelines.

Recent Advancements in Recombinant Monoclonal Antibodies

  • Bispecific Antibodies: Target two antigens simultaneously, improving therapeutic outcomes in diseases like cancer and autoimmune disorders.
  • Antibody-Drug Conjugates (ADCs): Combine mAbs with cytotoxic agents for targeted delivery of chemotherapeutics to diseased cells.
  • Fc Engineering: Enhances effector functions such as ADCC and CDC or extends serum half-life. Example: Modified glycosylation to improve NK cell-mediated killing.
  • Nanobody Fusion Constructs: Single-domain antibodies (VHH) fused with Fc regions for enhanced tissue penetration and half-life.
  • Fully Human Antibodies: Derived from transgenic mice or phage display libraries, offering reduced immunogenicity.

GenScript Services and Products for Recombinant Monoclonal Antibodies

Conclusion

Recombinant monoclonal antibodies have transformed medicine, diagnostics, and biotechnology, offering unprecedented specificity and therapeutic potential. Their versatility in design and function, coupled with advances in recombinant DNA technology, ensures their continued growth as a cornerstone of modern biopharmaceuticals. As production methods evolve, recombinant mAbs are poised to address even greater challenges in precision medicine and global health.


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Service and Products

Antibody Production Services

Comprehensive custom antibody production services including monoclonal and polyclonal antibody production services with industry leading turnaround times.

Polyclonal Antibody Services

The fastest custom polyclonal antibody production services in the industry with unmatched guarantees.

Custom Monoclonal Antibody Development Services

Developing custom monoclonal antibodies with standard or fully custom protocols including everything from antigen synthesis to antibody scale-up options.

Phospho-Specific Antibody Services

Guaranteed ELISA titer of ≥ 1:64,000 and < 10% cross reactivity with non-phospho peptide.

Immunoassay Development Services

Our custom immunoassay development service offering comprehensive high-throughput assay development with fast turnaround and high efficiency.

Large-scale Antibody Manufacturing

Our large-scale antibody manufacturing services offer polyclonal and monoclonal antibody production of gram quantities for industrial antibody yields.

COVID-19 Reagent Antibodies

On demand SARS-CoV-2 control mAbs ideal for diagnostics, therapeutic, and vaccine development.

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