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February 1, 2000The Journal of Immunology

Structural Correlates of an Anticarcinoma Antibody: Identification of Specificity-Determining Residues (SDRs) and Development of a Minimally Immunogenic Antibody Variant by Retention of SDRs Only

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Authors

MTMidori TamuraDMDiane E. MilenicMIMakoto Iwahashi

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Overview

Preclinical study demonstrates that grafting only specificity-determining residues prevents anti-variable reactivity in patient sera, suggesting a path to minimize antibody immunogenicity.

Key Points

  • To identify specificity-determining residues essential for antigen binding in the anticarcinoma antibody CC49 and engineer a minimally immunogenic antibody variant.
  • Constructed a panel of antibody variants through genetic manipulation of the murine CC49 hypervariable regions.
  • Assayed the variants for relative antigen-binding affinity and reactivity against sera collected from patients previously immunized with murine CC49.
  • Mapped the hypervariable region residues of CC49 that directly mediate antigen binding versus those that form immunogenic idiotopes recognized by patient antibodies.
  • Generated variant HuCC49V10 containing exclusively the specificity-determining residues grafted onto human frameworks, which eliminated binding to anti-variable region antibodies in patient sera while retaining antigen-binding capacity.

Cite This Study

Tamura et al. (2000) studied this question.

synapsesocial.com/papers/6a0ef41937aeb0126447baa3https://doi.org/10.4049/jimmunol.164.3.1432
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