Immunization with a recombinant MAGE-A3 protein after high-dose therapy for myeloma.
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.
Szmania
Susann
S
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Gnjatic
Sacha
S
Tricot
Guido
G
Stone
Katie
K
Zhan
Fenghuang
F
Moreno
Amberly
A
Thuro
Brad
B
Melenhorst
Jos
J
Barrett
John
J
Shaughnessy
John
J
Old
Lloyd J
LJ
Barlogie
Bart
B
Brichard
Vincent G
VG
van Rhee
Frits
F
D019264:Adoptive Transfer / Q000379:methods*; D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D009363:Neoplasm Proteins / Q000276:immunology / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D014427:Twins / Q000276:immunology; D014611:Vaccination / Q000379:methods
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015234:HLA-A Antigens; C053029:HLA-A*68 antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D007371:Interferon-gamma