title: CD30 is a potential therapeutic target in malignant mesothelioma.
abstract: CD30 is a cytokine receptor belonging to the TNF superfamily (TNFRSF8) that acts as a regulator of apoptosis. The presence of CD30 antigen is important in the diagnosis of Hodgkin disease and anaplastic large cell lymphoma. There have been sporadic reports of CD30 expression in nonlymphoid tumors, including malignant mesothelioma. Given the remarkable success of brentuximab vedotin, an antibody-drug conjugate directed against CD30 antigen, in lymphoid malignancies, we undertook a study to examine the incidence of CD30 in mesothelioma and to investigate the ability to target CD30 antigen in mesothelioma. Mesothelioma tumor specimens (N = 83) were examined for CD30 expression by IHC. Positive CD30 expression was noted in 13 mesothelioma specimens, primarily those of epithelial histology. There was no significant correlation of CD30 positivity with tumor grade, stage, or survival. Examination of four mesothelioma cell lines (H28, H2052, H2452, and 211H) for CD30 expression by both FACS analysis and confocal microscopy showed that CD30 antigen localized to the cell membrane. Brentuximab vedotin treatment of cultured mesothelioma cells produced a dose-dependent decrease in cell growth and viability at clinically relevant concentrations. Our studies validate the presence of CD30 antigen in a subgroup of epithelial-type mesothelioma tumors and indicate that selected mesothelioma patients may derive benefit from brentuximab vedotin treatment.
authors.affiliation: Division of Hematology and Oncology, Case Comprehensive Cancer Center and University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Snehal
authors.initials: S
authors.lastname: Dabir
authors.affiliation: Division of Pathology, Case Comprehensive Cancer Center and University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Adam
authors.initials: A
authors.lastname: Kresak
authors.affiliation: Division of Pathology, Case Comprehensive Cancer Center and University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Michael
authors.initials: M
authors.lastname: Yang
authors.affiliation: Division of Biostatistics, Case Comprehensive Cancer Center and University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Pingfu
authors.initials: P
authors.lastname: Fu
authors.affiliation: Division of Hematology and Oncology, Case Comprehensive Cancer Center and University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Gary
authors.initials: G
authors.lastname: Wildey
authors.affiliation: Division of Hematology and Oncology, Case Comprehensive Cancer Center and University Hospitals Case Medical Center, Cleveland, Ohio. afshin.dowlati@case.edu.
authors.forename: Afshin
authors.initials: A
authors.lastname: Dowlati
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D000079963:Brentuximab Vedotin; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology; D017730:Ki-1 Antigen / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008654:Mesothelioma / Q000188:drug therapy / Q000378:metabolism*; D000086002:Mesothelioma, Malignant; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D018796:Immunoconjugates; D017730:Ki-1 Antigen; D000079963:Brentuximab Vedotin