CONVICT: sentencing Cancer cells to death through ONcolytic Virotherapy and modulation of the Immune Checkpoint TIGIT

Immunotherapy to combat cancer has become well-established alongside conventional cancer therapies in the last decade. Notably, classical immune checkpoint inhibition (ICI) for PD-1/PD-L1 and CTLA-4 using monoclonal antibodies (mAbs) has achieved significant clinical impact in various cancers. Despite the promising clinical results, a large group of patients do not benefit from this therapy. Therefore, novel immune checkpoints (e.g. LAG-3 and TIGIT) and combination therapies are being studied.

To further enhance patient outcome, research has focused on cancer immunization to complement immune checkpoint therapies, such as oncolytic virotherapy. Oncolytic viruses (OVs) are promising therapeutics due to their ability to achieve tumor specific lysis, to release danger signals and tumor antigens to activate the immune system. In this regard, we propose to improve the effect of the already existing OVICI combination therapy using nanobody (Nb)-mediated blockade of the novel immune checkpoint TIGIT.
Moreover, we will build an innovative oncolytic mimetic platform by engineering lentiviral vectors to specifically infect and kill cancer cells and release in situ-produced TIGIT blocking Nbs. To better monitor the treatment response and achieve personalized treatment, we will develop an entirely novel diagnostic radiotracer for TIGIT as well.
When successful the antiTIGIT Nbs in combination with virotherapy could change how cancer is managed