Understanding CD30 biology and therapeutic targeting: a historical perspective providing insight into future directions

C. A. van der Weyden, S. A. Pileri, Andrew L Feldman, J. Whisstock, H. M. Prince

Research output: Contribution to journalReview article

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)e603
JournalBlood Cancer Journal
Volume7
Issue number9
DOIs
StatePublished - Sep 8 2017

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Hodgkin Disease
Anaplastic Large-Cell Lymphoma
Cutaneous T-Cell Lymphoma
Immunoconjugates
Peripheral T-Cell Lymphoma
Bacterial Toxins
Phase II Clinical Trials
Clinical Trials, Phase I
Tumor Necrosis Factor Receptors
B-Cell Lymphoma
Hematologic Neoplasms
Standard of Care
Tumor Biomarkers
Anti-Idiotypic Antibodies
Neoplasms
Cell Survival
Up-Regulation
Therapeutics
History
Lymphocytes

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Understanding CD30 biology and therapeutic targeting : a historical perspective providing insight into future directions. / van der Weyden, C. A.; Pileri, S. A.; Feldman, Andrew L; Whisstock, J.; Prince, H. M.

In: Blood Cancer Journal, Vol. 7, No. 9, 08.09.2017, p. e603.

Research output: Contribution to journalReview article

van der Weyden, C. A. ; Pileri, S. A. ; Feldman, Andrew L ; Whisstock, J. ; Prince, H. M. / Understanding CD30 biology and therapeutic targeting : a historical perspective providing insight into future directions. In: Blood Cancer Journal. 2017 ; Vol. 7, No. 9. pp. e603.
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