Brentuximab Vedotin Induces Cell Death, Protects Healthy Cells in Breast Cancer Treatment

Brentuximab vedotin (Adcetris; Pfizer) demonstrated potent activity against malignant cells, suggesting its potential as a therapeutic agent to treat patients with estrogen receptor-positive (ER+) and triple-negative breast cancer (TNBC). In the study, published in Scientific Reports, brentuximab vedotin promoted apoptosis and impaired the healing capacity of cancer cells.¹

Depiction of targeted therapy and cancer cell | Image Credit: © Hikmet - stock.adobe.com

Breast cancer is one of the most common cancers around the world, accounting for about 25% of all cancer diagnoses and 16% of mortalities in women. Advancements in treatment approaches have improved outcomes; however, there are various subtypes of breast cancer that prove more challenging to treat. In clinical and real-world trials, targeted therapies have demonstrated superior capabilities in identifying and targeting specific molecular targets in ER+ breast cancer and TNBC.¹

Brentuximab vedotin is a CD30-targeting monoclonal antibody drug conjugate (ADC) designed to induce cell death. It was approved by the FDA on March 20, 2018, for treatment of adults with previously untreated stage 3 or 4 classical Hodgkin lymphoma in combination with chemotherapy. This indication was expanded to treatment of pediatric patients in 2022.^2,3

In the study, researchers aimed to evaluate the therapeutic application of brentuximab vedotin in breast cancer, as well as determine the efficacy of utilizing CD30 as a molecular target. This was done through assessing the cytotoxic effects of the agent across 5 cell lines: normal human skin fibroblasts (HSF), 3 breast cancer cell lines (MCF-7, MDA-MB-231, and T-47D), and histiocytic lymphoma (U-937). HSF was used as a negative control, while U-937 served as a positive control.¹

Brentuximab vedotin treatment was administered at 0, 24, 48, and 72 hours with cell viability assessed at each interval. According to the data, HSF cells experienced limited toxicity, exhibiting over 70% minimal viability loss. In the MCF-7 and MDA-MB-231 cell lines, the researchers observed time-dependent reduction in viability with a significant decline by 72 hours. T-47D cells also showed decreases in viability; however, this happened at a slower rate. These data indicated brentuximab vedotin’s efficacy in both ER+ breast cancer and TNBC.¹

The researchers also reported the capabilities of brentuximab vedotin to impair the migration and healing ability of cancer cells, which was found using wound healing assays. Cell cycle analysis showed that the agent halted mitosis in MCF-7 and MDA-MB-231 cell lines without affecting normal HSF, potentially reducing side effects. There were also significant increases in apoptosis, especially in late apoptosis in cancer lines by 72 hours.¹

These findings indicate brentuximab vedotin’s selective cytotoxicity against cancer cells while sparing normal cells, suggesting its potential as an effective therapeutic agent across breast cancer subtypes. The primary limitation of the study was the use of in vitro models, which may not capture the complexities of in vivo human tumors. This warrants continued studies to determine brentuximab vedotin’s safety and efficacy in this setting.

REFERENCES

1. Ezzat, A., Shafiek, M., Shawki, S. et al. Therapeutic potential of brentuximab vedotin in breast cancer and lymphoma via targeted apoptosis and gene regulation. Sci Rep. January 13, 2025. doi:10.1038/s41598-024-84744-y

2. Brentuximab vedotin. FDA. March 20, 2018. Accessed January 14, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/brentuximab-vedotin

3. FDA approves brentuximab vedotin in combination with chemotherapy for pediatric patients with classical Hodgkin lymphoma. News release. FDA. November 10, 2022. Accessed January 14, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brentuximab-vedotin-combination-chemotherapy-pediatric-patients-classical-hodgkin