Article


Cellular immune responses against CT7 (MAGE-C1) and humoral responses against other cancer-testis antigens in multiple myeloma patients

Nikoletta Lendvai1*, Sacha Gnjatic2, Erika Ritter2, Michael Mangone1, Wayne Austin1, Karina Reyner1, David Jayabalan3, Ruben Niesvizky4, Sundar Jagannath5, Nina Bhardwaj1, Selina Chen-Kiang3, Lloyd J. Old2 and Hearn Jay Cho1

1New York University Cancer Institute, New York University School of Medicine, New York, NY, USA

2The Ludwig Institute for Cancer Research, New York Branch, New York, NY, USA

3Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, USA

4Division of Hematology/ Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, NY, USA

5Multiple Myeloma Program, Bone Marrow and Blood Stem Cell Transplantation, St. Vincent's Comprehensive Cancer Center, New York, NY, USA

*Present address: Department of Medicine, Hematology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Communicated by: V Cerundolo

Keywords: human, multiple myeloma, CT antigens, cellular immunity, humoral immunity


Abstract

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.