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Related Experiment Videos

Engineering antibodies for therapy.

A Mountain1, J R Adair

  • 1Celltech Research, Celltech Ltd, Slough, UK.

Biotechnology & Genetic Engineering Reviews
|January 1, 1992
PubMed
Summary
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Rodent monoclonal antibodies (MAbs) cause immune responses, limiting cancer therapy. Humanization and antibody fragments improve MAb efficacy and targeting of potent agents to tumors, offering future cancer treatment potential.

Area of Science:

  • Biotechnology
  • Immunology
  • Oncology

Background:

  • Rodent monoclonal antibodies (MAbs) often elicit a Human Anti-Mouse Antibody (HAMA) response, reducing therapeutic efficacy and causing toxicity.
  • This immunogenicity is a significant challenge for MAb-based cancer therapies, particularly for MAb-cytotoxic agent conjugates.

Purpose of the Study:

  • To review strategies for overcoming MAb immunogenicity and enhancing MAb-based cancer therapy.
  • To evaluate the potential of antibody engineering, including humanization and antibody fragments, for improved drug delivery and therapeutic outcomes.

Main Methods:

  • Review of existing literature on MAb engineering and therapeutic applications.
  • Analysis of immunogenicity data and strategies like chimerization and full humanization.

Related Experiment Videos

  • Evaluation of antibody fragments for pharmacokinetics, biodistribution, and tumor targeting.
  • Assessment of MAb-based delivery of cytotoxic agents, radioisotopes, and drugs.

    • Main Results:

    • Humanization significantly reduces MAb immunogenicity, though full humanization's long-term impact requires further data.
    • Antibody fragments show promise for optimizing MAb pharmacokinetics and biodistribution, especially for tumor detection and therapy.
    • Conjugation technology for delivering potent cytotoxic agents and radioisotopes via MAbs is advancing, with encouraging clinical data for hematologic malignancies.

    Conclusions:

    • Humanized antibody fragments are a promising approach for targeted cancer therapy.
    • MAb targeting of potent cytotoxic agents offers improved therapeutic ratios for solid tumors.
    • Further clinical data will clarify the long-term efficacy of fully humanized MAbs in overcoming immunogenicity.