3.1.2　Agonistic Antibodies: Activating the Effecto...

As mentioned above, mAbs have been so far essentially designed to block receptors (antagonistic function) or to induce the death of the cells targeted.Another potential mechanism that may be exploited to generate therapeutic tumour immunity is the ability of some mAbs to behave as surrogate ligands, providing agonistic signals to immunostimulatory receptors.This is the case for urelumab, an anti-CD137 mAb developed by BMS which is currently being tested in solid tumors and lymphoma.CD137 (also known as 4-1-BB) is a co-stimulatory receptor expressed on the membrane of activated T- and NK-cells.The ability of agonistic anti-CD137 mAb, either alone or in combination, to generate anti-tumor immune responses is currently being explored in clinical trials.Another agonistic mAb targeting the costimulatory molecule CD134 (a.k.a OX40) is currently tested in phase I/II clinical trials in combination with radiation therapy for patients with metastatic breast cancer and in combination with radiation and chemotherapy in metastatic prostate cancer.Other agonistic mAbs are under early development targeting costimulatory molecules such as HVEM (herpesvirus entry mediator, aka Tumor necrosis factor receptor superfamily member 14 or TNFRSF14), CD27 and GITR (glucocorticoid-induced tumor necrosis factor receptor) [10, 22].(https://www.daowen.com)