Compugen’s Cancer Immunotherapy Program Targets TIGIT Immune Checkpoint

Compugen’s Cancer Immunotherapy Program Targets TIGIT Immune Checkpoint

Compugen has revealed details of its cancer immunotherapy program for TIGIT – internally known as CGEN-15137 – an immune checkpoint that has recently gained attention from the immuno-oncology industry.

TIGIT, a T-cell immune-receptor with Ig and ITIM domains, has the potential to inhibit both T-cell and NK-cell activation when bound to its ligand poliovirus receptor (PVR).

TIGIT has the ability to inhibit both T-cell and NK-cell activation when bound to its ligand poliovirus receptor (PVR). Moreover, TIGIT has been observed to inhibit T-cell activation due to its ability to disrupt DNAM1 co-stimulatory signals.

TIGIT gained the industry’s attention when it was demonstrated in mice studies that its antibody antagonists could potentially inhibit the growth of tumors, when combined with the PD1 pathway blockade.

The company presented the TIGIT program at the Annual Meeting of the Society of Immunotherapy for Cancer (SITC 2016) in November. At the presentation, Compugen disclosed details of the program, which is based on data that shows that a PVRIG (a protein that in humans is encoded by the PVRIG gene) immune checkpoint could represent a new inhibitory component of the TIGIT mode of action. TIGIT and PVRIG represent two distinct arms of the same biological pathway.

Grounded on the hypothesis that a dual blockade of PVRIG and TIGIT should lead to a more robust T-cell response, and to a possibly better anti-tumor immune response, researchers tested both TIGIT and PVRIG activity in in vitro studies.

This assessment found that dual blockade indeed increased the activity of tumor-infiltrating T-cells, in comparison to the levels achieved by only blocking TIGIT or PVRIG.

The new therapeutic antibody program targeting TIGIT was thus initiated by Compugen, to complement the PVRIG program, based on these findings.

“We are excited to disclose our therapeutic program for TIGIT, an immuno-oncology target of high industry interest,” Anat Cohen-Dayag, PhD, president and CEO of Compugen, said in a press release. “Our efforts to date have demonstrated the potential enhanced efficacy of a combination treatment of a TIGIT antibody together with COM701 (PVRIG),” she said.

“Based on this and our experimental data demonstrating synergistic activation of T-cells, we believe there is a significant added value to developing both arms of this potential combination therapy,” Cohen-Dayag said. “Currently, we are in the process of developing a therapeutic antibody for CGEN-15137/TIGIT, and expect to select the lead antibody for this target by end of the first quarter of 2017.”

“It is becoming clearer that more closely tailored combination therapies will be able to address … a higher percentage of cancer patients. We therefore have high expectations for our diversified portfolio of novel immune checkpoint candidates,” Cohen-Dayag added.

Information on Compugen’s TIGIT discovery can be found in the October 2009 issue of the Proceedings of National Academy of Sciences (PNAS 2009).