Cellular immune responses against CT7 (MAGE-C1) and humoral responses against other cancer-testis antigens in multiple myeloma patients.
The type I melanoma antigen gene (MAGE) proteins CT7 (MAGE-C1) and MAGE-A3 are commonly expressed in multiple myeloma (MM), and their expression correlates with increased plasma cell proliferation and poor clinical outcome. They belong to the cancer-testis antigen (CTAg) group of tumor-associated proteins, some of which elicit spontaneous immune responses in cancer patients. CT7 and MAGE-A3 are promising antigenic targets for therapeutic tumor vaccines in myeloma; therefore, it is critical to determine if they are immunogenic in MM patients. We analyzed cellular and humoral immune responses against CTAgs in patients with plasma cell dyscrasias: MM, monoclonal gammopathy of undetermined significance (MGUS), and Waldenström's macroglobulinemia (WM). Bone marrow lymphocytes from two of four untreated MM patients exhibited CT7-specific cellular immune responses as measured by an autologous cellular immunity assay, the first such immune response to CT7 to be reported in cancer patients. Sera from 24 patients were screened by ELISA for humoral immune responses to CTAgs. Two patients with MM demonstrated positive titers, one for MAGE-A1 and the other for SSX1. These data demonstrate that CTAgs, particularly CT7, are immunogenic in MM patients and merit further exploration as targets of immunological therapy in MM.
Lendvai
Nikoletta
N
New York University Cancer Institute, New York University School of Medicine, New York, NY, USA.
Gnjatic
Sacha
S
Ritter
Erika
E
Mangone
Michael
M
Austin
Wayne
W
Reyner
Karina
K
Jayabalan
David
D
Niesvizky
Ruben
R
Jagannath
Sundar
S
Bhardwaj
Nina
N
Chen-Kiang
Selina
S
Old
Lloyd J
LJ
Cho
Hearn Jay
HJ
D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000951:Antigens, Neoplasm; C072013:MAGEA3 protein, human; C110905:MAGEC1 protein, human; D009363:Neoplasm Proteins