A Trinity Nano-Vaccine System with Spatiotemporal Immune Effect for the Adjuvant Cancer Therapy after Radiofrequency Ablation

Cancer vaccine gains great attention with the advances
in tumor
immunology and nanotechnology, but its long-term efficacy is restricted
by the unsustainable immune activity after vaccination. Here, we demonstrate
the vaccine efficacy is negatively correlated with the tumor burden.
To maximum the vaccine-induced immunity and prolong the time-effectiveness,
we design a priming–boosting vaccination strategy by combining
with radiofrequency ablation (RFA), and construct a bisphosphonate
nanovaccine (BNV) system. BNV system consists of nanoparticulated
bisphosphonates with dual electric potentials (BNV(+&−)),
where bisphosphonates act as the immune adjuvant by blocking mevalonate
metabolism. BNV(+&−) exhibits the spatial and temporal
heterogeneity in lymphatic delivery and immune activity. As the independent
components of BNV(+&−), BNV(−) is drained to the
lymph nodes, and BNV(+) is retained at the injection site. The alternately
induced immune responses extend the time-effectiveness of antitumor
immunity and suppress the recurrence and metastasis of colorectal
cancer liver metastases after RFA. As a result, this trinity system
integrated with RFA therapy, bisphosphonate adjuvant, and spatiotemporal
immune effect provides an orientation for the sustainable regulation
and precise delivery of cancer vaccines.

随着肿瘤免疫学与纳米技术的进步，癌症疫苗受到广泛关注，但其接种后免疫活性难以持续，限制了长期疗效。本研究证实，疫苗效力与肿瘤负荷呈负相关。为最大化疫苗诱导的免疫应答并延长时效，我们设计了联合射频消融（radiofrequency ablation, RFA）的初免-加强疫苗接种策略，并构建了双膦酸盐纳米疫苗（bisphosphonate nanovaccine, BNV）系统。该BNV系统由携带双电位的纳米级双膦酸盐（BNV(+&−)）组成，其中双膦酸盐可通过阻断甲羟戊酸代谢发挥免疫佐剂作用。BNV(+&−)在淋巴递送与免疫活性层面表现出时空异质性：作为BNV(+&−)的独立组分，BNV(−)可引流至淋巴结，而BNV(+)则滞留于注射部位。交替诱导的免疫应答延长了抗肿瘤免疫的时效，并抑制了射频消融后结直肠癌肝转移的复发与转移。综上，这一整合了RFA治疗、双膦酸盐佐剂与时空免疫效应的三位一体系统，为癌症疫苗的可持续调控与精准递送提供了新方向。