Cavrotolimod, a Nanoparticle Toll-like Receptor 9 Agonist, Inhibits Tumor Growth and Alters Immune Cell Composition in Mouse Models of Skin Cancer

Herein, we produced and characterized cavrotolimod (formerly AST-008), a 20–30 nanometer-diameter immunostimulatory spherical nucleic acid targeting Toll-like receptor 9 (TLR9), for the treatment of solid tumors such as advanced Merkel cell carcinoma (MCC) and cutaneous squamous cell carcinoma (CSCC). Cavrotolimod agonizes TLR9 to produce T-helper 1 (Th1)-type immune responses. We studied cavrotolimod in two mouse models: in an MCC model (using cavrotolimod monotherapy) and in a CSCC model (monotherapy and combination therapy). In the MCC model, a 7.5 mg/kg intratumoral (IT) dose of cavrotolimod elicited tumor growth inhibition (TGI) of up to 68%. In the CSCC model, treatment with 5.0 and 7.5 mg/kg cavrotolimod alone and in combination with an anti-PD-1 antibody produced tumor growth inhibition (TGI = 33–42%). Cavrotolimod was well-tolerated, induced immune cell population changes in the tumors and blood consistent with TGI, and reduced tumor burden in MCC and CSCC mouse models. Cavrotolimod is a promising nanoparticle therapy for these advanced solid tumors.