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

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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.