CD83 is a new potential biomarker and therapeutic target for Hodgkin lymphoma
Ziduo Li,
Xinsheng Ju,
Kenneth Lee,
Candice Clarke,
Jennifer L. Hsu,
Edward Abadir,
Christian E. Bryant,
Suzanne Pears,
Neroli Sunderland,
Scott Heffernan,
Annemarie Hennessy,
Tsun-Ho Lo,
Geoffrey A. Pietersz,
Fiona Kupresanin,
Phillip D. Fromm,
Pablo A. Silveira,
Con Tsonis,
Wendy A. Cooper,
Ilona Cunningham,
Christina Brown,
Georgina J. Clark,
Derek N.J. Hart
Affiliations
Ziduo Li
Dendritic Cell Research, ANZAC Research Institute, Sydney, Australia;Sydney Medical School, University of Sydney, Australia
Xinsheng Ju
Dendritic Cell Research, ANZAC Research Institute, Sydney, Australia;Sydney Medical School, University of Sydney, Australia
Kenneth Lee
Sydney Medical School, University of Sydney, Australia;Department of Anatomical Pathology, Concord Repatriation General Hospital, Sydney, Australia
Candice Clarke
Department of Anatomical Pathology, Concord Repatriation General Hospital, Sydney, Australia
Jennifer L. Hsu
Dendritic Cell Research, ANZAC Research Institute, Sydney, Australia;Sydney Medical School, University of Sydney, Australia
Edward Abadir
Dendritic Cell Research, ANZAC Research Institute, Sydney, Australia;Sydney Medical School, University of Sydney, Australia
Christian E. Bryant
Dendritic Cell Research, ANZAC Research Institute, Sydney, Australia;Institute of Haematology, Royal Prince Alfred Hospital, Sydney, Australia
Suzanne Pears
Animal Facility, Royal Prince Alfred Hospital, Sydney, Australia
Neroli Sunderland
Animal Facility, Royal Prince Alfred Hospital, Sydney, Australia
Scott Heffernan
Animal Facility, Royal Prince Alfred Hospital, Sydney, Australia
Annemarie Hennessy
Animal Facility, Royal Prince Alfred Hospital, Sydney, Australia
Tsun-Ho Lo
Dendritic Cell Research, ANZAC Research Institute, Sydney, Australia;Sydney Medical School, University of Sydney, Australia
Geoffrey A. Pietersz
Burnet Institute, Melbourne, Australia;Baker Heart and Diabetes Institute, Melbourne, Australia
Fiona Kupresanin
Dendritic Cell Research, ANZAC Research Institute, Sydney, Australia
Phillip D. Fromm
Dendritic Cell Research, ANZAC Research Institute, Sydney, Australia;Sydney Medical School, University of Sydney, Australia
Pablo A. Silveira
Dendritic Cell Research, ANZAC Research Institute, Sydney, Australia;Sydney Medical School, University of Sydney, Australia
Con Tsonis
Dendritic Cell Research, ANZAC Research Institute, Sydney, Australia
Wendy A. Cooper
Sydney Medical School, University of Sydney, Australia;Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia;School of Medicine, University of Western Sydney, Australia
Ilona Cunningham
Department of Haematology, Concord Repatriation General Hospital, Sydney, Australia
Christina Brown
Sydney Medical School, University of Sydney, Australia;Institute of Haematology, Royal Prince Alfred Hospital, Sydney, Australia
Georgina J. Clark
Dendritic Cell Research, ANZAC Research Institute, Sydney, Australia;Sydney Medical School, University of Sydney, Australia
Derek N.J. Hart
Dendritic Cell Research, ANZAC Research Institute, Sydney, Australia;Sydney Medical School, University of Sydney, Australia
Chemotherapy and hematopoietic stem cell transplantation are effective treatments for most Hodgkin lymphoma patients, however there remains a need for better tumor-specific target therapy in Hodgkin lymphoma patients with refractory or relapsed disease. Herein, we demonstrate that membrane CD83 is a diagnostic and therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node biopsies. CD83 from Hodgkin lymphoma tumor cells was able to trogocytose to surrounding T cells and, interestingly, the trogocytosing CD83+T cells expressed significantly more programmed death-1 compared to CD83−T cells. Hodgkin lymphoma tumor cells secreted soluble CD83 that inhibited T-cell proliferation, and anti-CD83 antibody partially reversed the inhibitory effect. High levels of soluble CD83 were detected in Hodgkin lymphoma patient sera, which returned to normal in patients who had good clinical responses to chemotherapy confirmed by positron emission tomography scans. We generated a human anti-human CD83 antibody, 3C12C, and its toxin monomethyl auristatin E conjugate, that killed CD83 positive Hodgkin lymphoma cells but not CD83 negative cells. The 3C12C antibody was tested in dose escalation studies in non-human primates. No toxicity was observed, but there was evidence of CD83 positive target cell depletion. These data establish CD83 as a potential biomarker and therapeutic target in Hodgkin lymphoma.
