Creation of a lymphatic drug delivery system: controlling distant metastasis and immune-related adverse events

本财政年度，我们旨在研究免疫检查抑制剂(ICI)在治疗过程中对IRAE的淋巴转移和发病发展的抑制作用，我们在以下方面做了工作：(1)评价免疫检查点抑制剂(ICI)通过淋巴给药系统(LDDS)局部控制和预防肺转移的疗效。将肿瘤细胞接种于MXH10/Mo/LPR小鼠的髂下淋巴结(SiLN)，于接种后第4天和第8天将CTLA4注入接种肿瘤的SiLN。10 mg/kg CTLA4单侧接种组可抑制SiLN内肿瘤生长，而双侧接种组可抑制SiLN和肺组织的生长。(2)为了改善治疗效果，降低IRE，我们通过LDDS使用ICI的抗癌药物。将肿瘤细胞接种到MXH10/Mo/LPR小鼠的SiLN中，并在不同的接种顺序和天数下对肿瘤接种的SiLN进行阿霉素和CTLA4联合化疗免疫治疗，以优化最佳组合。

This fiscal year, we aim to investigate immune check inhibitor (ICI) against lymph node metastasis and onset development of irAE during treatment, we worked on the following issues.(1) Evaluation of treatment outcome of immune check point inhibitor (ICI) for local control and prevention of lung metastasis via lymphatic drug delivery system (LDDS). MXH10/Mo/lpr mice were inoculated with tumor cells into the subiliac lymph node (SiLN), and CTLA4 was injected into tumor-inoculated SiLN on day 4 and 8 after inoculation. 10 mg/kg CTLA4 was able to inhibit tumor growth in the SiLN for one-side inoculation group, whereas SiLN and lung in both-side inoculation group with reduced irAEs such as sialadenitis and pneumonia.(2) To improve treatment outcome with reduced irAE, we are using anticancer drug with ICI through the LDDS. MXH10/Mo/lpr mice were inoculated with tumor cells into the SiLN, and chemoimmunotherapy is performed with combination of Doxorubicin and CTLA4 into tumor-inoculated SiLN on different sequences and days to optimize perfect combination.