CD83 is a promising biomarker and therapeutic target in Hodgkin Lymphoma — ASN Events
  1. Schedule
  2. Poster Session One & Burnet Oration Cocktail Function
  3. CD83 is a promising biomarker and therapeutic target in Hodgkin Lymphoma

CD83 is a promising biomarker and therapeutic target in Hodgkin Lymphoma (#142)

Edward Abadir 1 2 , Kenneth Lee 2 3 , Ziduo Li 1 2 , Candice Clarke 3 , Wendy A Cooper 2 4 5 , Robin E Gasiororwski 1 2 6 , Xinsheng Ju 1 2 , Christina Brown 2 7 , Christian E Bryant 1 7 , Jennifer L Hsu 1 2 , Barbara Fazekas de St Groth 2 8 , P Mark Hogarth 9 , Ilona Cunningham 1 2 6 , Georgina J Clark 1 2 , Derek NJ Hart 1 2
  1. ANZAC Research Institute, Camperdown, NSW, Australia
  2. Sydney Medical School, Sydney, NSW, Australia
  3. Department of Anatomical Pathology, Concord Repatriation General Hospital, Concord, NSW, Australia
  4. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  5. School of Medicine, University of Western Sydney, Sydney, NSW, Australia
  6. Department of Haematology, Concord Repatriation General Hospital, Concord, NSW, Australia
  7. Institute of Haematology, Royal Prince Alfred Hospital , Camperdown, NSW, Australia
  8. Charles Perkins Centre, Sydney, NSW, Australia
  9. Burnet Institute, Melbourne, VIC, Australia

Chemotherapy and hematopoietic stem cell transplantation are effective treatments for the majority of patients with Hodgkin lymphoma (HL), however current regimes are highly toxic and there remains a need for better tumor-specific targeted therapy in patients with refractory or relapsed disease. Membrane CD83 is a novel diagnostic and therapeutic target that is highly expressed in HL cell lines and HL Reed-Sternberg cells (29/35 HL patient lymph node biopsies). CD83 from HL tumor cells can trogocytose surrounding T cells, the trogocytosing CD83+T cells expressed significantly more PD-1 compared to CD83- T cells. Soluble CD83 (sCD83) was elevated in all patients analysed with active HL. T cell proliferation is inhibited by sCD83 and an anti-CD83 antibody partially reversed this inhibitory effect. The elevated levels of sCD83 detected in HL patient sera with active disease returned to normal in patients who had a complete response to chemotherapy as confirmed by positron emission tomography-computed tomography (PET-CT)-scans. We generated a human anti-human CD83 antibody, 3C12C, and a toxin monomethyl auristatin E (MMAE) conjugate (3C12C-MMAE). Both the unaltered antibody and its MMAE conjugate killed CD83 positive HL cell lines but not CD83 negative cells. The 3C12C antibody was tested in dose escalation studies of non- human primates. No toxicity was observed but there was evidence of in vivo efficacy with depletion of CD83 positive cells.  These findings establish CD83 as excellent potential biomarker and therapeutic target in HL.

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