肿瘤细胞治疗研究
英文原题：Valrubicin-loaded immunoliposomes targeting antigens on immunosuppressive cells to circumvent resistance to cancer immunotherapy.
Valrubicin-loaded immunoliposomes targeting antigens on immunosuppressive cells to circumvent resistance to cancer immunotherapy.
我们开发了负载valrubicin的免疫脂质体（Val-ILs），这是一种基于纳米颗粒的疗法，旨在靶向促进癌症免疫逃逸的免疫抑制细胞。
我们开发了负载valrubicin的免疫脂质体（Val-ILs），这是一种基于纳米颗粒的疗法，旨在靶向促进癌症免疫逃逸的免疫抑制细胞。在小鼠体内静脉给药后的体内筛选确定了九个相关表面靶点，包括已知的免疫调节标志物（LAG-3和VEGFR2）以及特征尚不明确的候选靶点（CD11b、CD64、TIM1、CD200R3、CD204、CD49b和SIGLEC-F）。在肿瘤微环境中，Val-ILs治疗广泛降低了这些抗原在免疫抑制细胞群上的表达，包括肿瘤相关巨噬细胞、髓源性抑制细胞、调节性T细胞和辅助性T细胞17，以及固有抗肿瘤细胞如肿瘤相关NK 细胞和肿瘤浸润性树突状细胞。在四种小鼠癌症模型中，两种响应性模型（T和B淋巴瘤）和两种耐药性模型（原位乳腺癌和肺癌），装饰有针对这九个靶点抗体的Val-ILs显著增强了抗PD-1疗效。这种联合治疗提高了CD4+和CD8+TIL（肿瘤浸润淋巴细胞）的存在，将肿瘤相关巨噬细胞重编程为M1样表型，并改善了肿瘤控制及转移减少。
We develop valrubicin-loaded immunoliposomes (Val-ILs), a nanoparticle-based therapy designed to target immunosuppressive cells that promote immune evasion in cancer. In vivo screening following intravenous administration in mice identifies nine relevant surface targets, including known immunoregulatory markers (LAG-3 and VEGFR2) and not-well-characterized candidates (CD11b, CD64, TIM1, CD200R3, CD204, CD49b, and SIGLEC-F). Within the tumor microenvironment, Val-ILs treatment broadly reduces the expression of these antigens on immunosuppressive populations, including tumor-associated macrophages, myeloid-derived suppressor cells, regulatory T cells, and T helper 17 cells, as well as on innate anti-tumor cells such as tumor-associated natural killer cells and tumor-infiltrating dendritic cells. Across four murine cancer models, two responsive (T and B lymphomas) and two resistant (orthotopic breast and lung cancers), Val-ILs decorated with antibodies against the nine targets significantly enhance anti-PD-1 efficacy. This combination boosts the presence of CD4 + and CD8 + tumor-infiltrating lymphocytes, reprograms tumor-associated macrophages toward an M1-like phenotype, and improves tumor control and metastasis reduction.
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