Targeted delivery of boron depots containing immune adjuvant to achieve efficient cancer therapy via a combination of BNCT and cancer vaccine

Despite the recent progress in cancer treatment, the 5-year survival rates for many types of cancer are still below 30%. The current therapeutic modalities are subject to significant limitations such as systemic toxicity, low efficacy and lack of long-term sustainability. Physicians often resort to a combinational therapeutic strategy, such as chemotherapy followed by surgical resection then immunotherapy, that requires many courses of treatments with elongated inpatient care time and high cost. In this article, we introduced iBNCT, immune-enhanced Boron Neutron Capture Therapy, as a new cancer treatment modality that combines the benefits of tumor targeting therapy, radiotherapy and immunotherapy. Sustained-release 10B drugs were formulated with an immune cell adjuvant, and delivered into tumors using microneedle jet injection devices. Pharmacokinetics data revealed a reversed 10B distribution, e.g., a high concentration in tumors and a low concentration in blood and main organs. One-time delivery of 30 mg 10B/kg led to an intratumor 10B concentration of over 300 ppm in a 24 h window and a T/N ratio up to 4000. Upon neutron irradiations, model-estimated tumor cell killing rate of 99.6% was achieved. More importantly, the in-situ formed neoantigens, with the stimulation of the immune cell adjuvant, triggered a very strong adaptive immune response and produced a high-level tumor antigen-specific T cells in a controllable fashion. The high intratumor 10 B concentration along with the exceptional T/N ratio provides the basis for effective tumor cell killing, reduces the requirement for high neutron flux, and significantly improves irradiation-safety with less burden on in-person radioactive protection. The in-situ generated tumor antigen-specific T cells could be collected, amplified and infused back into patients to provide an observable anti-tumor immune memory. We believe that iBNCT, with short treatment time and low cost, could potentially become a cancer therapeutic modality that replaces the current combination therapeutic strategies.