Preclinical Development – Biomolecular
2019 PharmSci 360
T cell-dependent bispecific molecules represent a promising class of therapeutic molecules for the treatment of cancer. Unlike therapeutic mAb or ADC, the MOA of the bispecific is dependent upon simultaneous engagement of both the tumor cell and T cell. Co-engagement of both cells leads to formation of cellular synapse, which then induces activation of T cell through the T cell receptor leading to lysis of the target tumor cell. In this study, an in vitro assay was established using an early marker of T cell activation as a surrogate for cellular synapse formation. Data derived from the in vitro assay was used to develop a mechanism-based model to simultaneously assess the effect of various factors on cellular synapse formation. The modeling framework can guide the design and development of T cell-dependent bispecific molecules.