Bi-specific antibodies to direct cytotoxic T cells to TRAIL-R2 expressing tumors


-Istituto Nazionale Tumori-

Patent relating to the construction of a bi-specific antibody structured as scdb.

A new bi-specific antibody has been constructed, structured as a “single chain diabody” (scdb) capable of simultaneously recognizing and binding the TRAIL-R2 receptor on the tumor and the CD3 activating molecule on T cells.

Unlike other bispecific antibody structuring, the scdb conformation allows T-cells to be activated only when an immunocytolytic synapse is formed with the cancer cell hooked by the specific anti-tumor portionTRAIL-R2, thus avoiding non-specific T activation with consequent adverse effects such as “cytokinic storm” or destruction of normal cells.

In addition to binding TRAIL-R2 to a wide range of tumor types (melanoma, ovarian cancer, breast cancer, lymphomas), the scdb acts as both a TRAIL agonist, inducing apoptosis of the cancer cell, and activating the cytotoxicity of T cells, by binding to CD3 and subsequent activation with release of soluble death mediators. This activity was found to be dose-dependent and -specific to cancer cells expressing TRAIL-R2.

Patent (WO2016EP65577) – filed in 2015

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