针对异质实体癌的癌症治愈免疫反应需要在抗原狂热但免疫抑制的肿瘤微环境（TME）中启动协调的免疫激活。然而，可塑性 TME 和免疫激活药物较差的全身耐受性是产生治疗性抗癌免疫反应的根本障碍。在这里，我们引入了 CarboCell 技术，通过形成肿瘤内持续药物释放库来克服这些障碍，该库在 TME 内选择性地提供高有效负载的免疫刺激药物。 CarboCell从而诱导免疫细胞训练和极化的热点，并进一步驱动和维持肿瘤引流淋巴结处于抗癌和免疫激活状态。从机制上讲，这会转化癌组织，从而产生全身抗癌免疫反应。 CarboCell 可以通过标准细针技术注射，并具有固有的成像对比度，可确保准确的瘤内定位。特别是，我们在此报告了双药 CarboCell 在雌性小鼠临床前肿瘤模型中持续释放 Toll 样受体 7/8 激动剂和转化生长因子-β 抑制剂的治疗性能。© 2024。作者（ s）。

Cancer curing immune responses against heterogeneous solid cancers require that a coordinated immune activation is initiated in the antigen avid but immunosuppressive tumor microenvironment (TME). The plastic TME, and the poor systemic tolerability of immune activating drugs are, however, fundamental barriers to generating curative anticancer immune responses. Here, we introduce the CarboCell technology to overcome these barriers by forming an intratumoral sustained drug release depot that provides high payloads of immune stimulatory drugs selectively within the TME. The CarboCell thereby induces a hot spot for immune cell training and polarization and further drives and maintains the tumor-draining lymph nodes in an anticancer and immune activated state. Mechanistically, this transforms cancerous tissues, consequently generating systemic anticancer immunoreactivity. CarboCell can be injected through standard thin-needle technologies and has inherent imaging contrast which secure accurate intratumoral positioning. In particular, here we report the therapeutic performance for a dual-drug CarboCell providing sustained release of a Toll-like receptor 7/8 agonist and a transforming growth factor-β inhibitor in preclinical tumor models in female mice.© 2024. The Author(s).