Named Grant:

The Harvey and Gloria Kaylie Foundation Research Professorship Grant

About the Investigator:

Born in Jerusalem, Israel, Prof. Ofer Mandelboim received his Ph.D. from the Weizmann Institute
of Science, performed postdoctoral research at Harvard University as a Fulbright Scholar, and is
now a full Professor of Molecular Immunology at the Hebrew University of Jerusalem.

About the Research:

Immunotherapy of cancer is one of the most promising advancements made in the past decade.
However, despite its success, there is still an urgent need to find additional approaches for
fighting tumors. This is because: 1) Not all cancers respond to immunotherapies; 2) Within a
cancer that presents susceptibility to immunological treatments, not all patients will respond;
3) Combination treatment is predicted to have greater efficacy; and 4) Tumors are likely to
develop escape variants.

TIGIT, an inhibitory molecule discovered by our group, is expressed by various immune cell
subsets, inhibiting their activities. It is also expressed by regulatory T cells (or Tregs); but, on
these cells TIGIT functions as a stimulating receptor that enhances their activity. The known TIGIT
ligands (a molecule that binds to another, usually larger, molecule) are mainly PVR and nectin2,
which are overexpressed on many different tumors. Thus, blocking TIGIT interaction with its
ligands by using blocking antibodies is one of the most promising new treatments for cancer.
Phase I clinical trials in which blocking anti-TIGIT antibodies are being used, primarily in
melanoma patients, are currently being conducted. However, in order to understand the full
TIGIT potential and to select the appropriate patients, the full spectrum of TIGIT ligands should be
identified.

In this proposal, Prof. Mandelboim and his team will use two new ligands for TIGIT that they have
discovered. They propose to characterize the interaction between these to ligands and TIGIT and to develop blocking antibodies that can be used as new checkpoint inhibitors.