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

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.

• Authors: Man Li, Yuting Yang, Chaoqun Xu, Jiaojie Wei, Yingke Liu, Xingli Cun, Qianwen Yu, Xian Tang, Sheng Yin, Zhirong Zhang, Qin He
• Journal: The AAPS journal (AAPS J) Vol. 21 Issue 2 Pg. 18 (01 11 2019) ISSN: 1550-7416 [Electronic] United States
• PMID: 30635795 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antineoplastic Agents, Immunological
• B7-H1 Antigen
• Cd274 protein, mouse
• Galactosylceramides
• alpha-galactosylceramide
• Paclitaxel

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Antineoplastic Agents, Immunological (pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• B7-H1 Antigen (antagonists & inhibitors, immunology)
• Cell Line, Tumor (transplantation)
• Female
• Galactosylceramides (administration & dosage)
• Immune Tolerance (drug effects)
• Lung Neoplasms (drug therapy, immunology, secondary)
• Melanoma, Experimental (drug therapy, immunology, secondary)
• Mice
• Paclitaxel (administration & dosage, immunology)
• Skin Neoplasms (drug therapy, immunology, pathology)
• T-Lymphocytes, Cytotoxic (drug effects)