ES425: A Promising Therapeutic Approach for Targeting Triple-Negative Breast Cancer through T-Cell Redirection

The study focuses on the development of a novel therapeutic agent, ES425, which is a bispecific ADAPTIR molecule designed to target triple-negative breast cancer (TNBC), a type of cancer with limited treatment options. ES425 is engineered to direct T-cell cytotoxicity towards tumor cells that express ROR1, an antigen found in TNBC and other cancers.

In vitro tests were conducted to evaluate the cytotoxic activity of ES425 on ROR1-positive and ROR1-negative cell lines using human T cells and peripheral blood mononuclear cells. The results were measured through chromium release assays, and T-cell activation and proliferation were assessed using flow cytometry.

Pharmacokinetics of ES425 were studied in NOD/SCID gamma mice after a single intravenous dose, with serum concentrations measured over time to determine the drug's elimination half-life. The in vivo efficacy of ES425 was tested in mice implanted with ROR1-positive TNBC cells, with tumor growth measured by volume.

The findings indicate that ES425 effectively redirected T cells to target ROR1-positive cells in vitro at low concentrations and demonstrated a serum half-life of approximately 7 days in mice. Moreover, ES425 significantly inhibited tumor growth in mouse xenografts and improved overall survival in the tested models.

The research concludes that ES425 shows promise as a potential therapeutic agent for TNBC and other malignancies, warranting further investigation. The study was presented at the 107th Annual Meeting of the American Association for Cancer Research and published in the Cancer Research journal.