Immunotherapy in multiple myeloma: Id-specific strategies suggested by studies in animal models

Cancer Immunol Immunother. 2004 Sep;53(9):759-69. doi: 10.1007/s00262-004-0504-1. Epub 2004 Apr 15.


Multiple myeloma (MM) cells produce monoclonal immunoglobulin (Ig) which serves as a truly tumor-specific antigen. The tumor-specific antigenic determinants are localized in the variable (V)-regions of the monoclonal Ig and are called idiotopes (Id). We review here the evidence obtained in a T-cell receptor (TCR) transgenic mouse model that Id-specific, MHC class II-restricted CD4+ T cells play a pivotal role in immunosurveillance and eradication of MHC class II-negative MM cells. In brief, monoclonal Ig secreted by MM cells is endocytosed and processed by antigen-presenting cells (APCs) in the tumor. Such tumor-resident dendritic cell APCs in turn present Id peptide on their class II molecules to Id-specific CD4+ T cells which become activated and indirectly kill the MHC class II-negative myeloma cells. However, if the Id-specific CD4+ cells fail to eliminate the MM cells during their initial encounter, the increasing number of tumor cells secretes so much monoclonal Ig that T-cell tolerance to Id is induced. Extending these findings to MM patients, Id-specific immunotherapy should be applied at a time of minimal residual disease and when new Id-specific T cells have been educated in the thymus, like after high-dose chemotherapy and autologous stem cell transplantation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Dendritic Cells / immunology
  • Disease Models, Animal*
  • Histocompatibility Antigens Class II / immunology
  • Immunization*
  • Immunoglobulin Idiotypes / immunology*
  • Immunotherapy*
  • Lymphocyte Activation / immunology
  • Mice
  • Multiple Myeloma / immunology
  • Multiple Myeloma / therapy*


  • Antigens, Neoplasm
  • Histocompatibility Antigens Class II
  • Immunoglobulin Idiotypes