Immunization with a recombinant MAGE-A3 protein after high-dose therapy for myeloma

J Immunother. Nov-Dec 2007;30(8):847-54. doi: 10.1097/CJI.0b013e318158fcff.

Abstract

MAGE-A3 is frequently expressed in high-risk multiple myeloma (MM). We immunized a healthy donor with MAGE-A3 protein formulated in AS02B to transfer immunity to her identical twin, diagnosed with MAGE-A3-positive MM. After a melphalan 200 mg/m syngeneic peripheral blood stem cell transplant, primed donor cells collected after immunizations were transferred and followed by repeated patient immunizations. MAGE-A3 immunizations were well tolerated. Strong MAGE-A3-specific antibody, cytotoxic T-lymphocyte (CTL), and T-helper responses were induced in both twins. A humoral response was transferred to the patient with the donor peripheral blood stem cells and increased by booster immunization. The CTL response targeted a previously undescribed HLA-A*6801 binding MAGE-A3115-123 peptide. MAGE-A3115-123 CTLs were detected in the patient more than 1 year after the last immunization. Multiple T-helper cellular responses were detected with the dominant response to an HLA-DR11 restricted MAGE-A3 epitope. The patient remains in remission 2.5 years after the second transplant. This report shows for the first time that immunization of a healthy donor with a defined cancer-testis protein induces immune responses that can be transferred and expanded posttransplant in the recipient. MAGE-A3 immunization may be a useful adjunct to high dose melphalan-based peripheral blood stem cell transplant, providing a new therapeutic option for high-risk MM.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / methods*
  • Adult
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / therapeutic use*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Female
  • Flow Cytometry
  • HLA-A Antigens / immunology
  • Humans
  • Immunophenotyping
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology
  • Multiple Myeloma / immunology
  • Multiple Myeloma / therapy*
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / therapeutic use*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Treatment Outcome
  • Twins / immunology
  • Vaccination / methods

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • HLA-A Antigens
  • HLA-A*68 antigen
  • MAGEA3 protein, human
  • Neoplasm Proteins
  • Interferon-gamma