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

Nikoletta Lendvai^1*, 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

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.