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Title: Understanding CD30 biology and therapeutic targeting: a historical perspective providing insight into future directions.
Epworth Authors: Prince, Miles
Other Authors: van der Weyden, Carrie
Pileri, Stefano
Feldman, Andrew
Whisstock, James
Keywords: CD30
Hematopoietic Malignancies
Brentuximab Vedotin
Tumor Marker
Therapeutic Target
Tumor Necrosis Factor Receptor
Cell Survival
Hodgkin Lymphoma
Peripheral T-Cell Lymphoma
Cutaneous T-Cell Lymphoma
Disease Control
Anaplastic Large Cell Lymphoma
Future Directions
Cancer Services Clinical Institute, Epworth HealthCare, Victoria, Australia
Issue Date: Sep-2017
Publisher: Nature Publishing Group
Citation: Blood Cancer J. 2017 Sep 8;7(9):e603
Abstract: CD30 is a member of the tumor necrosis factor receptor superfamily. It is characteristically expressed in certain hematopoietic malignancies, including anaplastic large cell lymphoma and Hodgkin lymphoma, among others. The variable expression of CD30 on both normal and malignant lymphoid cells has focused research efforts on understanding the pathogenesis of CD30 upregulation, its contribution to lymphomagenesis through anti-apoptotic mechanisms, and its effect on cell survival. Given the restriction of CD30 to certain tumor types, the logical extension of this has been to attempt to exploit it as a therapeutic target. The efficacy of naked anti-CD30 antibodies in practice was, however, modest. Moreover, combinations with bacterial toxins and radioimmunoconjugates have also had limited success. The development of the antibody-drug compound brentuximab vedotin (BV), however, has rejuvenated interest in CD30 as a tumor target. Phase I and II clinical trials in Hodgkin lymphoma, peripheral T-cell lymphoma, cutaneous T cell lymphoma, and even CD30-expressing B-cell lymphomas, have shown the compound is well tolerated, but more importantly, able to deliver meaningful disease control even in patients with multiply relapsed or refractory disease. FDA approval has been granted for its use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. A recent phase III trial of BV in cutaneous T-cell lymphoma has confirmed its superiority to standard of care therapies. In this manuscript, we explore the history of CD30 as a tumor marker and as a therapeutic target, both in the laboratory and in the clinic, with a view to understanding future avenues for further study.
DOI: 10.1038/bcj.2017.85
PubMed URL:
ISSN: 2044-5385
Journal Title: Blood Cancer Journal
Type: Journal Article
Affiliated Organisations: Department of Haematology, Peter McCallum Cancer Centre, Melbourne, Victoria, Australia
Haematopathology Unit, European Institute of Oncology, Milan, Italy
Bologna University School of Medicine, Bologna, Italy
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia
Type of Clinical Study or Trial: Review
Appears in Collections:Cancer Services

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