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

本财政年度，我们的目标是研究免疫抑制剂（ICI）对淋巴结转移和治疗期间irAE发病的影响，我们研究了以下问题。(1)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治疗结果评价。将肿瘤细胞接种到MXH 10/Mo/lpr小鼠的髂下淋巴结（SiLN）中，并在接种后第4天和第8天将CTLA 4注射到肿瘤接种的SiLN中。10 mg/kg CTLA 4能够抑制单侧接种组的SiLN中的肿瘤生长，而双侧接种组的SiLN和肺中的肿瘤生长，并且减少了irAE如涎腺炎和肺炎。(2)为了改善治疗结果，减少irAE，我们通过LDDS使用抗癌药物与ICI。将肿瘤细胞接种到MXH 10/Mo/lpr小鼠的SiLN中，并在不同的顺序和天数对肿瘤接种的SiLN中使用阿霉素和CTLA 4的组合进行化学免疫治疗，以优化完美的组合。

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.