Project 462235

Accumulating evidence indicates that SLAMF7, a molecule expressed at the surface of "innate" immune cells known as macrophages and NK cells, is a useful target for new anticancer immunotherapies. Amongst these data, it was shown that the anti-SLAMF7 monoclonal antibody (MAb) elotuzumab (Empliciti) is highly effective in the treatment of multiple myeloma, a blood cell cancer in humans that universally expresses high levels of SLAMF7. In this proposal, we want to understand better how SLAMF7 influences innate immune cell functions against cancer. We also wish to elucidate how this activity is controlled by agents that regulate inflammation in the tumor micro-environment. Lastly, we want to ascertain the mechanism of action and therapeutic usefulness of MAb Z10, a novel unique anti-SLAMF7 MAb that augments SLAMF7 anti-cancer activity. This MAb is proprietary and was recently discovered in our laboratory. In combination, these studies will provide a better understanding of how SLAMF7 can be used as a target to treat human cancer.