Key Laboratory of Drug Targeting, Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Section 3, Southern Renmin Road, Chengdu, 610041, People's Republic of China.
Sichuan Academy of Chinese Medicine Science, Chengdu, 610041, People's Republic of China.
AAPS J. 2019 Jan 11;21(2):18. doi: 10.1208/s12248-018-0289-3.
Chemoimmunotherapy with chemotherapeutics and immunoadjuvant inhibits tumor growth by activating cytotoxic T cells. However, this process also upregulates the expression of PD-1/PD-L1 and consequently leads to immune suppression. To maximize the anti-tumor immune responses and alleviate immunosuppression, PD-L1 antibody was combined with paclitaxel (PTX) and the immunoadjuvant α-galactosylceramide (αGC), which were coencapsulated into pH-sensitive TH peptide-modified liposomes (PTX/αGC/TH-Lip) to treat melanoma and lung metastasis. Compared to treatment with PD-L1 antibody or PTX/αGC/TH-Lip alone, the combination of PD-L1 antibody and PTX/αGC/TH-Lip further elevated the tumor-specific cytotoxic T cell responses and promoted apoptosis in tumor cells, leading to enhanced anti-tumor and anti-metastatic effects. In adoptive therapy, PD-L1 antibody further alleviated immunosuppression and enhanced the anti-tumor effect of CD8 T cells. The combination of PD-L1 antibody and chemoimmunotherapy PTX/αGC/TH-Lip provides a promising strategy for enhancing treatment for melanoma and lung metastasis.
化疗免疫疗法结合化疗药物和免疫佐剂通过激活细胞毒性 T 细胞来抑制肿瘤生长。然而，这一过程也会上调 PD-1/PD-L1 的表达，从而导致免疫抑制。为了最大限度地提高抗肿瘤免疫反应并减轻免疫抑制，将 PD-L1 抗体与紫杉醇（PTX）和免疫佐剂α-半乳糖神经酰胺（αGC）联合包封到 pH 敏感的 TH 肽修饰的脂质体（PTX/αGC/TH-Lip）中，以治疗黑色素瘤和肺转移。与单独使用 PD-L1 抗体或 PTX/αGC/TH-Lip 相比，PD-L1 抗体和 PTX/αGC/TH-Lip 的联合使用进一步提高了肿瘤特异性细胞毒性 T 细胞反应，并促进了肿瘤细胞的凋亡，从而增强了抗肿瘤和抗转移作用。在过继疗法中，PD-L1 抗体进一步减轻了免疫抑制，并增强了 CD8 T 细胞的抗肿瘤作用。PD-L1 抗体与化疗免疫疗法 PTX/αGC/TH-Lip 的联合使用为增强黑色素瘤和肺转移的治疗提供了一种有前途的策略。
