Generation of a human anti-idiotypic antibody that mimics the GD2 antigen

J Immunol. 1993 Sep 15;151(6):3390-8.

Abstract

In a phase 1 trial, patients with metastatic melanoma received the anti-GD2 murine mAb 14G2a. All patients developed human anti-14G2a antibodies including anti-Id antibodies. Peripheral blood MNCs from one such patient were fused with the murine myeloma cell line Ag8. Four human anti-14G2a secreting hybridomas were generated and the mAb product of one of the hybridomas was characterized. The human mAb 4B5 (hu-IgG, lambda) binds to the variable region of murine 14G2a (anti-Id). The 4B5 binds to the antigen-combining site of 14G2a and inhibits its binding to GD2 expressing Mel-21 cells. Rabbits were immunized with the human anti-Id 4B5. Sera from the immunized rabbits demonstrated anti-4B5 antibodies and anti-Mel-21 and anti-GD2 reactivity. Furthermore, rabbit sera competitively inhibited binding of 14G2a to Mel-21 cells. Rabbits immunized with 4B5 developed a DTH response when challenged with 4B5 antibody and Mel-21 cells. These studies demonstrate that the human anti-Id 4B5 mimics the GD2 antigen and is capable of eliciting both a humoral and cellular anti-GD2 immune response. This antibody could be potentially used as a human anti-Id vaccine in patients with malignant melanoma.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / immunology*
  • Antibodies, Monoclonal / immunology
  • Gangliosides / immunology*
  • Humans
  • Hypersensitivity, Delayed / immunology
  • Immunization
  • Immunotherapy, Active
  • Melanoma / immunology
  • Melanoma / therapy
  • Mice
  • Rabbits

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Gangliosides
  • ganglioside, GD2