CD30 is a potential therapeutic target in malignant mesothelioma

Our plain-English summary of CD30 is a potential therapeutic target in malignant mesothelioma, by S. Dabir, A. Kresak, M. Yang, et al (Molecular Cancer Therapeutics, 2015).

The study

• Authors: S. Dabir, A. Kresak, M. Yang, P. Fu, G. Wildey, A. Dowlati
• Journal: Molecular Cancer Therapeutics
• Published: 2015;14(3):740-6
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

©2015 American Association for Cancer Research.

In plain English

This laboratory study asked whether malignant mesothelioma tumors carry CD30, a protein targeted by the lymphoma drug brentuximab vedotin. In public gene-expression databases, the authors found the highest CD30 levels in mesothelioma among solid-tumor cell lines, excluding lymphomas. They then stained 83 mesothelioma tumor specimens from the National Mesothelioma Virtual Bank. Thirteen of 83 (15.6%) were CD30-positive, mostly of epithelial histology. Positivity was 19.7% in epithelioid tumors versus 4.6% in biphasic and sarcomatoid tumors. The authors described this difference as approaching, but not reaching, statistical significance. CD30 positivity was not significantly linked to tumor grade, stage or overall survival. In mesothelioma cell lines, CD30 sat on the cell surface. In the two lines tested, the drug reduced cell growth and viability in a dose-dependent way, though less than in a lymphoma control line. The study did not examine asbestos exposure. The authors concluded that CD30 is present in a subgroup of epithelial-type mesothelioma tumors and that selected patients may benefit from the drug. They noted it is unclear how these laboratory results translate to patients.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study: analysis of public gene-expression databases, immunohistochemical staining of mesothelioma tumor tissue microarrays, and experiments on cultured mesothelioma cell lines treated with brentuximab vedotin
• Who was studied: 83 mesothelioma tumor specimens on tissue microarrays from the National Mesothelioma Virtual Bank, with survival data for 63 patients. Three further specimens came from the authors' hospital in Cleveland, Ohio. Four mesothelioma cell lines (H28, H2052, H2452, 211H) were bought from the ATCC. A lymphoma line (Karpas 299) served as positive control and a small cell lung cancer line (H526) as negative control.
• Exposure: No asbestos exposure was studied. The laboratory treatment studied was brentuximab vedotin, an anti-CD30 antibody-drug conjugate, given to cultured cells at 0.5, 15 and 60 micrograms per millilitre for mesothelioma cells. The text prints this as mg/mL, while the figure labels show µg/mL. The authors stated these doses are within the clinically achievable range.
• Main results:
  • In the Cancer Cell Line Encyclopedia database, mesothelioma cell lines showed the highest CD30 gene expression among solid-tumor cell lines, excluding lymphomas.
  • 13 of 83 mesothelioma tumor specimens (15.6%) were positive for CD30 by immunohistochemistry.
  • CD30-positive tumors were mainly of epithelial histology (12 of the 13).
  • CD30 positivity was 4.6% in the biphasic and sarcomatoid group versus 19.7% in the epithelioid group. The authors described this as approaching significance (P < 0.094); their significance threshold was P < 0.05.
  • CD30 positivity showed no significant correlation with tumor grade, stage or survival. Survival data were available for 63 patients.
  • In the mesothelioma cell lines, CD30 was located on the cell membrane, shown by confocal microscopy and flow cytometry.
  • Brentuximab vedotin caused a dose-dependent decrease in cell viability in the two mesothelioma cell lines tested (H2052 and H2452) after 48 hours, compared with untreated cells. Both were less sensitive than the lymphoma control cells, and the small cell lung cancer line H526 was largely resistant.
• The authors' conclusion: The authors concluded that their studies validate the presence of CD30 in a subgroup of epithelial-type mesothelioma tumors and indicate that selected mesothelioma patients may derive benefit from brentuximab vedotin treatment.
• Limitations the authors state:
  • It is unclear how far the drug sensitivity seen in cultured cells translates to drug sensitivity in mesothelioma patients.
  • The drug's effect in mesothelioma tumors may not simply correlate with CD30 positivity.
  • The cell lines were not authenticated.
  • Staging and grading data for the tumor cohort were incomplete.
  • The authors attributed their lower CD30-positive percentage, compared with another study, likely to scoring methods.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Cytokine, Apoptosis, Mesothelioma, Histology.

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