载脂蛋白 A1 修饰的多柔比星脂质体联合白细胞介素-21 增强小鼠乳腺癌化疗免疫治疗

Backgroud: Breast cancer is a prevalent malignancy among women, with triple-negative breast cancer (TNBC) comprising approximately 15-20% of all cases, possessing high invasiveness, drug resistance and poor prognosis. Chemotherapy, the main treatment for TNBC, is limited by toxicity and drug resistance. Apolipoprotein A1 modified doxorubicin liposome (ApoA1-lip/Dox) was constructed in our previous study, with promising anti-tumour effect and improved safety been proved.

However, during long-term administration, the problem of cumulative toxicity and insufficient tumour inhibition is still inevitable. Interleukin-21 is a small molecule protein secreted by T cells with various immune regulatory functions. IL-21 has significantly curative effects in numerous solid tumours, but it has the disadvantages of low response rate and short half-life. The combination of chemotherapy and immunotherapy has received increasing attention. Purpose: In this study, ApoA1 drug loading system and long-acting IL-21 are innovatively combined for tumour treatment.

Methods: We combined ApoA1-lip/Dox and IL-21 for treatment and evaluated their impact on tumor-infiltrating lymphocytes and CD8 + T and NK cell cytotoxicity. Results: Combined administration significantly improved the tumour-infiltrating lymphocytes and enhanced the cytotoxicity of CD8 + T and NK cells. The combination of ApoA1-lip/Dox and IL-21 exhibits significantly enhanced anti-tumour efficacy with lower toxicity of ApoA1-lip/Dox, providing a new strategy for TNBC treatment with enhanced anti-tumour response and reduced toxicity.