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Updated: Apr 22, 2026
Flow Cytometry-based Assay for the Monitoring of NK Cell Functions
Published on: October 30, 2016
Vorinostat downregulates CD30 and decreases brentuximab vedotin efficacy in human lymphocytes
Zainul S Hasanali1, Elliot M Epner2, David J Feith3
1Department of Microbiology and Immunology, Pennsylvania State University College of Medicine and Penn State Hershey Cancer Institute, Hershey, Pennsylvania.
Abstract:
With an increasing number of clinical trials looking at combination therapies in cancer, potential drug-drug interactions require particular attention. One such instance is the treatment of CD30(+) tumors after previous vorinostat (SAHA; suberoylanilide hydroxyamic acid) failure with the anti-CD30 antibody-drug conjugate brentuximab vedotin. Using B-, T-, and natural killer (NK)-cell lines in vitro, we demonstrate that SAHA downregulates the expression of CD30 and lowers the efficacy of subsequent brentuximab vedotin treatment if baseline CD30 levels are reduced by 50% or more. Interestingly, low-dose SAHA treatment that maintained 50% or more of basal CD30 expression followed by subsequent treatment with brentuximab vedotin led to enhanced antitumor activity. The downregulation of CD30 was short lived upon SAHA removal, suggesting that allowing SAHA washout may circumvent any interactions with subsequent drug therapies. Our findings confirm the requirement of CD30 for brentuximab vedotin efficacy and suggest that combination treatment with SAHA in CD30(dim) tumors may decrease efficacy. Combination treatment in highly CD30(+) tumors, however, increases efficacy and warrants further consideration as a new treatment paradigm.
Insights
Vorinostat (SAHA) can decrease brentuximab vedotin efficacy by reducing CD30 levels in cancer cells. However, low-dose SAHA may enhance antitumor activity, suggesting careful dosing is crucial for combination cancer therapy.
Area of Science:
- Oncology
- Pharmacology
- Immunotherapy
Background:
- Combination cancer therapies are increasingly common, necessitating careful evaluation of drug-drug interactions.
- Vorinostat (SAHA) and brentuximab vedotin are used in treating CD30-expressing tumors, but their combined use requires understanding potential interactions.
Purpose of the Study:
- To investigate the in vitro effects of vorinostat (SAHA) on CD30 expression and its impact on the efficacy of subsequent brentuximab vedotin treatment.
- To determine optimal conditions for combining SAHA and brentuximab vedotin for enhanced antitumor activity.
Main Methods:
- Utilized B-, T-, and natural killer (NK)-cell lines for in vitro experiments.
- Assessed CD30 expression levels following SAHA treatment.
- Evaluated the efficacy of brentuximab vedotin after varying SAHA pre-treatment conditions.
Main Results:
- SAHA significantly downregulated CD30 expression, reducing brentuximab vedotin efficacy when baseline CD30 levels dropped by 50% or more.
- Low-dose SAHA, maintaining CD30 levels, enhanced antitumor activity when combined with brentuximab vedotin.
- CD30 downregulation by SAHA was transient, suggesting washout periods could mitigate drug interactions.
Conclusions:
- SAHA's impact on CD30 expression is critical for brentuximab vedotin efficacy.
- Combining SAHA with brentuximab vedotin may decrease efficacy in CD30-dim tumors but enhance it in highly CD30+ tumors.
- This suggests a potential new treatment paradigm for CD30-expressing cancers, dependent on CD30 expression levels.
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