Cancer-Testis (CT) antigen expression in AL amyloidosis Meeting Abstract

Authors: Rosenzweig, M. A.; Landau, H.; Jungbluth, A. A.; Hanson, N.; Frosina, D.; Arcila, M.; Comenzo, R. L.; Koehne, G.
Abstract Title: Cancer-Testis (CT) antigen expression in AL amyloidosis
Meeting Title: 52nd Annual Meeting of the American Society of Hematology (ASH)
Abstract: Cancer-testis (CT) antigens are a family of proteins normally expressed in immune privileged sites such as testicular germ cells and placenta, but are overexpressed in various malignant tumors (Scanlan et al. Immunological Rev. 2002). CT antigens are therefore useful markers of malignancy, as well as potential targets for antigen specific cancer immunotherapy. In multiple myeloma, CT 7, CT 10 and MAGE-A are homogenously expressed in up to 75% of cases, and their expression increases with disease stage and cell proliferation (Jungbluth et al. Blood, 2005). In addition, CT-7 and MAGE-A3 play a role in plasma cell proliferation and chemosensitivity (Atanackovic et al. Haematologica 2010). Immunogenicity of CT antigens is evidenced by spontaneous humoral responses against CT antigens in patients with multiple myeloma (Cohen et al. ASH abstract 2008). In addition, anti-CT antigen immune responses of donor derived T and B cells have been reported following allogeneic stem cell transplantation, suggesting CT antigens may serve as a natural target for a graft-versus myeloma effect (Atanackovic et al. Blood 2007). Systemic light-chain (AL) amyloidosis is a plasma cell dyscrasia related to multiple myeloma characterized by small numbers of non-proliferating, clonogenic plasma cells producing pathologic light chains. In this study, we investigated the expression of several CT antigens. in patients with AL amyloidosis to identify potential targets for immunotherapy and determine;heir prognostic significance. Methods: Fifteen cases of AL amyloidosis were studied employing Standard. IHC techniques on paraffin-embedded archival tissues. Presence of plasma cells was verified by CD138 immunostain. The following monoclonal antibodies (to the following CT Antigens) were used: mAb MA454 (MAGE-A1), 6C1 (several MAGE-A antigens), 57B (MAGE-A4), E978 (NY-ESO-1), CT7-33(CT7), CT10#5 (CT10), #25 (GAGE). Immunopositivity was graded based on the amount of IHC-positive plasma cells. Results: All 15 patients had a confirmed diagnosis Of AL amyloidosis with an average plasma cell burden of 12.7% of the cells in the marrow. Eighty-seven percent (13/15) had lambda disease and 13% (2/15) kappa disease. Organ involvement included kidney (N=7)), heart (N=8), peripheral nervous system (N=2), and GI/liver (N=2). Five patients (33%) had multi-organ involvement. All patients were treated uniformly with risk-adapted melphalan as their initial therapy. CT7 was present in 9/15 (60%) while CT10 was demonstrated in only 1/15 AL amyloid cases. Plasma cells did not stain with any, other anti-CT mAb. There were no significant differences with regard to organ involvement, response to treatment or prognosis and CT antigen positivity in this small Sample set. Discussion This is the first study identifying CT7 as the prevalent CT antigen in plasma cells of patients with AL amyloidosis. The almost exclusive presence of CT7. in AL amyloidosis may have clinical significance. Further studies are planned on additional samples to confirm the prevalence of CT7 expression in AL amyloidosis, determine its immunogenicity and further investigate prognostic implications. Additional studies are needed to determine the biology of CT antigens in AL amyloidosis and their value as a potential target for immunotherapy.
Keywords: disease prognosis; immunopositivity
Journal Title: Blood
Volume: 116
Issue: 21
Meeting Dates: 2010 Dec 4-7
Meeting Location: Orlando, FL
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2010-11-19
Start Page: 1652
End Page: 1653
Language: English
PROVIDER: biosis
PUBMED: 22276300
Notes: --- - Meeting Abstract: 4055 - 52nd Annual Meeting of the American-Society-of-Hematology (ASH) - Orlando, FL, USA - December 04 -07, 2010 - Amer Soc Hematol - "Source: Biosis"