Developing the next generation of cis-targeting macrophage-T cell cancer immunotherapies

Immunotherapy holds great promise for the curative treatment of millions of cancer patients, with a market size of over 100 billion USD today, which is expected to at least double in the next decade. Cancer immunotherapies are designed either to promote anti-tumor immune activity in the tumor microenvironment (TME), via molecules such as cytokines and antibodies, or to inhibit negative T cell signals induced by cancer and antigen-presenting cells (APCs) in the TME, an approach known as immune checkpoint blockade (ICB). Yet current immunotherapies have shown significant clinical success only against a limited number of cancers, for two major reasons: insufficient anti-tumor immune activation or severe side effects and toxicity as a result of nonspecific immune activation. We propose to overcome these two challenges through the development of a novel class of molecules capable of simultaneously modulating the myeloid and lymphoid immune cell compartments in the TME and generating a highly specific and extremely potent antitumor immune response. In this PoC grant, we seek to validate the ability to construct such dual-modulatory agents, which will provide us with the proof-of-concept for these technologies.