CD83 is a new potential biomarker and therapeutic target for Hodgkin lymphoma.
Haematologica
; 103(4): 655-665, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-29351987
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulinas
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Doença de Hodgkin
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Glicoproteínas de Membrana
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Biomarcadores Tumorais
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Antígenos CD
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Terapia de Alvo Molecular
Tipo de estudo:
Diagnostic_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Haematologica
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Austrália