A Novel Tri‐Functional Liposome Re‐Educates "Cold Tumor" and Abrogates Tumor Growth by Synergizing Autophagy Inhibition and PD‐L1 Blockade. Issue 11 (3rd February 2023)

• Record Type: Journal Article
• Authors: Zhou, Fei; Li, Xiaojiaoyang; Xue, Xiaoyong; Li, Shuo; Fan, Guifang; Cai, Yajie; Chang, Zihao; Qu, Jiaorong; Liu, Runping
• Is Part Of: Advanced healthcare materials. Volume 12:Issue 11(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-02-03
• Subjects: autophagy inhibition -- cold tumors -- cytotoxic lymphocyte infiltration -- liposomes -- PD‐L1 blocking peptides; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.202202757
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: Immunotherapy has been regarded as a breakthrough in cancer treatment and achieved great success. However, the poor response rate is still a formidable challenge of current immunotherapies, especially in solid tumors without sufficient infiltration of immune cells, also known as "cold tumor." SAR405 is a highly specific VPS34 inhibitor and has been suggested as a potential approach converting "cold tumor" into "hot tumor" by inhibiting autophagy. In this study, a tri‐functional doxorubicin (DOX) plus SAR405 liposome system is established and further modified with a novel anti‐PD‐L1 peptide JY4 for targeted delivery (DOX‐SAR‐JY4LIPO ). The data here demonstrate that in a lung cancer xenograft mouse model, by facilitating the tumoral enrichment of both SAR405 and DOX, DOX‐SAR‐JY4LIPO effectively increases the infiltration of cytotoxic lymphocytes in the tumor by synergizing DOX‐induced immunogenic cell death (ICD) and SAR405‐mediated upregulation of chemokines including CCL5 and CXCL10. As results, DOX‐SAR‐JY4LIPO significantly inhibits tumor growth, metastasis, and resurrection by re‐educating immunosuppressive tumor microenvironment. In conclusion, this study not only proves the concept of inhibiting autophagy for better immune infiltration in the tumor but also presents a novel tri‐functional liposomal system that overcomes the deficiencies of current therapies and holds great promise in cancer immunotherapy. Abstract : In the current study, a novel PD‐L1 targeting peptide is designed and evaluated and then a novel tri‐functional liposomal system (DOX‐SAR‐JY4LIPO ) is established that re‐educates "cold tumor" into "hot tumor." DOX‐SAR‐JY4LIPO not only increases immune cell recruitment by inhibiting autophagy pathway but also significantly inhibits tumor growth, metastasis, and resurrection, which holds great promise in cancer immunotherapy.