Well-established immunotherapy with R837-loaded boron neutron capture-shocked tumor cells

Abstract

Although boron neutron capture therapy (BNCT) has been regarded as a curative therapy for aggressive tumors, the frequency of tumor recurrence and metastasis remains high mainly due to the adventitious nature of the immune response. Here, we explore the process of the immune response cascade after BNCT and find that the rate-limiting step is antigen presentation. To overcome this barrier, we develop a carrier-free nano-boron agent (BN-R837 @PVP), comprising hydrophilic 10B-boron nitride nanostructures loading with an immune agonist imiquimod (R837). The nano-boron agent can be internalized and cloaked into tumor cells and then following neutron irradiation, obtain the R837-loaded BNCT-shocked tumor cells (BTCs). When the BTCs are injected subcutaneously, the antigen pool and R837 are co-delivered into the draining lymph nodes, boosting immune responses as well as preventing R837 from entering the systemic circulation. This eventually results in significant inhibition of distal tumor growth and metastasis with a high rate of complete tumor regression in vivo. Moreover, memory T lymphocytes exist in these immunized mice and exhibit potent long-term anti-tumor.