Research by Yotsumoto, et al. reported that the authors identified transmembrane proteins overexpressed specifically in SCLC with little or no expression in normal tissues and decided to focus on the cell adhesion molecule neurexin-1.
The work was published in Oncotarget.
The cell surface overexpression of NRXN1 was confirmed using flow cytometry in SCLC cell lines.
The combination of a primary anti-NRXN1 monoclonal antibody and a secondary ADC exhibited anti-tumour activity in SCLC cell lines.
Moreover, the knockout of NRXN1 in SHP77 cells resulted in a loss of the anti-tumour activity of NRXN1-mediated ADC therapy.
Thus, NRXN1 could be a novel target for ADC therapy for the treatment of SCLC that is worth further research.
Dr. Daiya Takai from The University of Tokyo Hospital and Dr. Takuma Yotsumoto from The University of Tokyo Graduate School of Medicine said, “Small cell lung cancer (SCLC) accounts for 10–15% of lung cancer, and its prognosis has remained relatively dismal for years.”
Considering the high sensitivity of SCLC to chemotherapy, the selective delivery of a cytotoxic agent using ADC could be a novel treatment strategy for SCLC.
Five ADCs have been approved by The Food and Drug Administration:
- – Brentuximab vedotin for Hodgkin lymphoma
- – Ado-trastuzumab emtansine for HER2-positive metastatic breast cancer
- – Inotuzumab ozogamicin for acute lymphoblastic leukaemia
- – Gemtuzumab ozogamicin for CD33-positive acute myeloid leukaemia, and
- – Trastuzumab deruxtecan for unresectable or metastatic HER2-positive breast cancer patients who have received two or more prior anti-HER2-based regimens in a metastatic setting.
In SCLC, DLL3, a cell surface Notch ligand that appears to be a direct downstream target of ASCL1, has been identified as a novel target for ADCs.
In this study, the authors aimed to identify novel molecular targets for ADCs in SCLC.
They herein report that NRXN1-mediated ADC exhibited anti-tumour activity in vitro, and thus NRXN1 could be a novel target of ADCs for SCLC.
The Takai/Yotsumoto Research Team concluded “we identified NRXN1 as a new target for ADCs by screening membrane proteins using a computational-biological approach. The combination of the primary anti-NRXN1 monoclonal antibody and the secondary ADC exhibited anti-tumour activity in an NRXN1-expression dependent manner. NRXN1 could be a novel potential target of ADCs for SCLC that is worth further research.”
Source: Impact Journals LLC