Despite the enormous therapeutic potential of immune checkpoint blockade (ICB), it benefits only a small subset of patients. Some chemotherapeutics can switch ‘immune-cold’ tumours to ‘immune-hot’ to synergize with ICB. However, safe and universal therapeutic platforms implementing such immune effects remain scarce. We demonstrate that sphingomyelin-derived camptothecin nanovesicles (camptothesomes) elicit potent granzyme-B- and perforin-mediated cytotoxic T lymphocyte (CTL) responses, potentiating PD-L1/PD-1 co-blockade to eradicate subcutaneous MC38 adenocarcinoma with developed memory immunity. In addition, camptothesomes improve the pharmacokinetics and lactone stability of camptothecin, avoid systemic toxicities, penetrate deeply into the tumour and outperform the antitumour efficacy of Onivyde. Camptothesome co-load the indoleamine 2,3-dioxygenase inhibitor indoximod into its interior using the lipid-bilayer-crossing capability of the immunogenic cell death inducer doxorubicin, eliminating clinically relevant advanced orthotopic CT26-Luc tumours and late-stage B16-F10-Luc2 melanoma, and achieving complete metastasis remission when combined with ICB and folate targeting. The sphingomyelin-derived nanotherapeutic platform and doxorubicin-enabled transmembrane transporting technology are generalizable to various therapeutics, paving the way for transformation of the cancer immunochemotherapy paradigm.

尽管免疫检查点封锁 (ICB) 具有巨大的治疗潜力，但它只对一小部分患者有益。一些化疗药物可以将“免疫冷”肿瘤转变为“免疫热”肿瘤以与 ICB 协同作用。然而，实现这种免疫作用的安全且通用的治疗平台仍然很少。我们证明，鞘磷脂衍生的喜树碱纳米囊泡（喜树碱体）可引发有效的颗粒酶 B 和穿孔素介导的细胞毒性 T 淋巴细胞 (CTL) 反应，增强 PD-L1/PD-1 共同阻断以根除具有记忆免疫力的皮下 MC38 腺癌。此外，喜树碱改善了喜树碱的药代动力学和内酯稳定性，避免了全身毒性，深入肿瘤并优于 Onivyde 的抗肿瘤功效。Camptothesome共加载吲哚胺2，3-双加氧酶抑制剂吲哚昔莫德利用免疫原性细胞死亡诱导剂多柔比星的脂质双层交叉能力进入其内部，消除临床相关的晚期原位 CT26-Luc 肿瘤和晚期 B16-F10-Luc2 黑色素瘤，并在以下情况下实现完全转移缓解结合 ICB 和叶酸靶向。鞘磷脂衍生的纳米治疗平台和多柔比星启用的跨膜转运技术可推广到各种疗法，为癌症免疫化疗范式的转变铺平了道路。当与 ICB 和叶酸靶向结合时实现完全转移缓解。鞘磷脂衍生的纳米治疗平台和多柔比星启用的跨膜转运技术可推广到各种疗法，为癌症免疫化疗范式的转变铺平了道路。当与 ICB 和叶酸靶向结合时实现完全转移缓解。鞘磷脂衍生的纳米治疗平台和多柔比星启用的跨膜转运技术可推广到各种疗法，为癌症免疫化疗范式的转变铺平了道路。