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Reshaping human antibodies for therapy.

L Riechmann1, M Clark, H Waldmann

  • 1MRC Laboratory of Molecular Biology, Cambridge, UK.

Nature
|March 24, 1988
PubMed
Summary
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Researchers reshaped a human antibody for serotherapy by incorporating rat antibody regions targeting human lymphocytes. The modified human antibody effectively targets lymphocytes, matching rat antibody efficacy in complement and surpassing it in cell-mediated lysis.

Area of Science:

  • Immunology
  • Biotechnology
  • Therapeutic Antibody Development

Background:

  • Human antibodies are crucial for serotherapy but can have limitations in targeting specific cells.
  • Rat antibodies can effectively target human cells, like lymphocytes, but their use in humans raises immunogenicity concerns.

Purpose of the Study:

  • To engineer a human antibody with enhanced efficacy for serotherapy against human lymphocytes.
  • To combine the targeting specificity of a rat antibody with the safety profile of a human antibody.

Main Methods:

  • Reshaping a human immunoglobulin G1 (IgG1) antibody by incorporating the six hypervariable regions from a rat anti-human lymphocyte antibody.
  • Evaluating the functional efficacy of the reshaped human antibody in complement-dependent cytotoxicity and cell-mediated lysis assays.

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Main Results:

  • The reshaped human IgG1 antibody demonstrated comparable efficacy to the original rat antibody in complement-mediated lysis of human lymphocytes.
  • The reshaped human antibody exhibited superior effectiveness compared to the rat antibody in cell-mediated lysis of human lymphocytes.

Conclusions:

  • Antibody reshaping is a viable strategy to create effective human therapeutic antibodies with specific targeting capabilities.
  • The engineered human antibody offers a promising alternative for serotherapy, potentially reducing immunogenicity while maintaining or improving therapeutic efficacy against human lymphocytes.