Bispecifics
Published on March 03, 2023
Oncolytic Adenovirus-Armed BiTEs “Could Overcome Limitations of BiTEs in Treatment of Solid Tumors”
by Eleanor Mayfield, ELS
Systemic use of bispecific T-cell engagers (BiTEs) to treat non-melanoma solid tumors has been limited by these agents' short half-life, as the high doses required to achieve sufficient tumor penetration can result in severe off-tumor toxicity. In a paper appearing in the March issue of Molecular Therapy Oncolytics, a research group in Finland describe a “proof of concept” for overcoming this limitation by arming BiTEs with an oncolytic adenovirus.
Akseli Hemminki, MD, PhD, and colleagues at the University of Helsinki “constructed and performed in vitro and in vivo validations of a human MUC1 targeting T cell engager-armed oncolytic adenovirus” dubbed TILT-321. The bispecific antibody expressed by TILT-321 “binds to the MUC1 antigen expressed by target tumor cells and CD3 receptors on the T cell surface.”
They found “that the cytotoxiciy of aMUC1aCD3-armed viruses in the presence of human T cells and MUC1-expressing cancer cells was higher than that of the controls, both in vitro and in vivo” and that the virus also replicates and lyses MUC1-negative HEK-293 cells. “These findings indicate that the virally encoded aMUC1aCD3-BsTe binds to its target tumor antigen and T cells simultaneously and mediates tumor cell killing, which is independent of major histocompatibility complex presentation,” the authors write.
They conclude that “the proposed technology could be preferentially beneficial for the treatment of solid tumors expressing MUC1. Our results lay the groundwork for clinical exploration, the translation of which is currently ongoing.”
- Basnet S, Santos JM, Quixabeira DCA, et al. Oncolytic adenovirus coding for bispecific T cell engager against human MUC-1 potentiates T cell response against solid tumors. Mol Ther Oncolytics. 2023 March 16;28:59-73. https://doi.org/10.1016/j.omto.2022.12.007
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