Blocking tumor-associated macrophage SIGLEC15 for solid tumors

INDICATION: Colorectal; melanoma; brain cancer; solid tumors

Patient sample, cell culture and mouse studies suggest inhibiting SIGLEC15 expressed on tumor-associated macrophages could help treat colorectal cancer, melanoma, glioblastoma and other solid tumors. In tissue samples from patients with colorectal cancer, bladder cancer, liver cancer, lung cancer or other solid tumors, SIGLEC15 expression was higher in tumors than in matched normal tissue. In mouse models of melanoma and glioblastoma, systemic or myeloid-specific SIGLEC15 knockout decreased tumor growth compared with normal SIGLEC15 expression and, in the melanoma model, increased survival. In a mouse model of colon cancer, macrophage-specific SIGLEC15 knockout decreased tumor growth. In the colon cancer model, an anti-SIGLEC15 mAb decreased lung metastases compared with vehicle. In the same model, another colon cancer model and the melanoma model, the anti-SIGLEC15 mAb decreased primary tumor growth. In the second colon cancer model, the anti-SIGLEC15 mAb plus Opdivo nivolumab increased tumor regression compared with either agent alone. Next steps by NextCure Inc. include Phase I/II testing of NC318, a humanized anti-SIGLEC15 mAb, to treat solid tumors...