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AACR 2022: Novel Microtubule-Targeting Agent Demonstrates Antilymphoma Activity

By: Lauren Harrison, MS
Posted: Thursday, April 21, 2022

Avanbulin, a microtubule-targeting agent, showed cytotoxic antilymphoma activity when tested in several different lymphoma cell lines. Avanbulin is the active portion of the prodrug lisavanbulin, and its anticancer activity is regulated by modulating the spindle assembly checkpoint. This research was presented at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 2575/14) by Francesco Bertoni, MD, of the Institute of Oncology Research, Bellinzona, Switzerland, and colleagues.

This study evaluated 26 lymphoma cell lines that were derived from activated B-cell–like and germinal center B-cell–type diffuse large B cell lymphoma. The cell lines were exposed to increasing doses of avanbulin, and cell proliferation was measured with an MTT assay. After being treated for 72 hours, the cells demonstrated antiproliferative activity of the compound. Although mutations in MYD88, TP53, or BCL2 seemed to have no effect among the different types of lymphoma cell lines , cell lines with a translocation in the MYC gene were less sensitive to avanbulin than the cells without the translocation.

Annexin V staining was performed to assess apoptosis induction in cells treated with 5, 10, 20, or 40 nM of avanbulin. Strong apoptosis induction was notable in 15 of the 17 cell lines tested at 20 nM and 40 nM by live cell imaging. For these 15 cell lines that underwent apoptosis, 8 demonstrated apoptotic induction within 24 hours of drug exposure, 6 between 24 and 48 hours of exposure, and 1 after 48 hours of exposure.

Cell-cycle analysis was performed after 24, 48, and 72 hours of exposure to 20 nM of avanbulin and confirmed cytotoxic effects of avanbulin in four diffuse large B cell lymphoma cell lines. There was sub-G0 accumulation already present at 24 hours in all four lines tested, with an increase over time. There was G2-M arrest in three of the four cell lines at 24 hours as well.

Disclosure: For a full list of authors’ disclosures, visit abstractsonline.com.


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