Immunotherapy, OSE-172, Seen to Be Safe and Effective in Mouse Models of Liver Cancer

Immunotherapy, OSE-172, Seen to Be Safe and Effective in Mouse Models of Liver Cancer

OSE-172, an immune checkpoint inhibitor that blocks immunosupressive cells in the tumor microenvironment, was shown to be safe in tumor mouse models and to induce strong remission rates when used in combination with other immunotherapies.

The findings were recently presented by Vanessa Gauttier, with OSE Immunotherapeutics, at the American Association for Cancer Research 2017 Annual Meeting in Washington, D.C. The poster was titled “Selective targeting of SIRP alpha induces potent memory anti-tumor immune responses without presenting haematological toxicity.”

“These new data demonstrate OSE-172 as having a differentiated safety and selective pharmacological profile which provides us with the opportunity to open various potential indications in immuno-oncology field for our new myeloid checkpoint inhibitor. We are currently actively preparing the next steps of its development towards clinical stage,” Bernard Vanhove, chief operating officer of OSE Immunotherapeutics in charge of R&D and International Scientific Collaborations, said in a press release.

Myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are two types of immune cells found inside the vast majority of solid tumors.

Although both MDSCs and macrophages are involved in the regulation of immune responses and in tissue repair in healthy individuals, these cells can be co-opted by cancer cells to start exerting suppressor functions, preventing other immune cells from attacking the tumor.

OSE-172 (Effi-DEM) is an antibody that blocks these pro-tumor suppressor cells and restores their effector function, allowing the mobilization of T-cells to the tumor. This is achieved by blocking the SIRP-alpha receptor, which is strongly expressed by both MDSCs and TAMs.

SIRP-alpha binds to CD47, which is often overexpressed in tumors, but agents targeting CD47 have recently shown blood toxicity, like anemia or reduced levels of platelets. For this reason, researchers sought to evaluate the preclinical safety and efficacy of OSE-172.

Giving high doses of OSE-172 to healthy or tumor-bearing mice did not affect red blood cells or platelets levels, while other anti-CD47 antibodies induced anemia within three days. Importantly, OSE-172 did not bind to SIRP-gamma, another member of the SIRP family that plays a role in T-cell proliferation.

The researchers also established the efficacy of OSE-172 alone and in combination with other immunotherapies, like a PD-L1 inhibitor and an anti-CD137 antibody, in a mouse model of hepatocellular carcinoma (HCC), the most common type of liver cancer.

While OSE-172 or PD-1 inhibition alone were mildly effective is this mouse model, combining both drugs induced durable remission in 60 percent of mice. Similar findings were seen when OSE-172 was combined with an antibody targeting the CD137 molecule, which induced an 80 percent long-term remission, compared to 25 percent and 26 percent in mice treated with either agent alone.

The team also found that transferring T-cells from mice cured with the combination regimens prevented the development of liver cancer in mice with the disease. This suggests that the treatment creates robust anti-tumor memory T-cells that can fight the tumor cells should the cancer return.