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AAPS J. 2019 Jan 11;21(2):18. doi: 10.1208/s12248-018-0289-3.

Tumor-Targeted Chemoimmunotherapy with Immune-Checkpoint Blockade for Enhanced Anti-Melanoma Efficacy.

Author information

1
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.
2
Sichuan Academy of Chinese Medicine Science, Chengdu, 610041, People's Republic of China.
3
West China School of Stomotology, Sichuan University, Chengdu, 610041, People's Republic of China.
4
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. qinhe@scu.edu.cn.

Abstract

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.

KEYWORDS:

PD-L1 antibody; chemo-immunotherapy; combined strategy; immunosuppression; α-galactosylceramide

PMID:
30635795
DOI:
10.1208/s12248-018-0289-3

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