Improved tumor accumulation and therapeutic efficacy of CTLA-4-blocking antibody using liposome-encapsulated antibody: In vitro and in vivo studies.

Cancer immunotherapies using monoclonal antibodies including cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) blocking monoclonal antibody have several drawbacks including lack of appropriate penetration to the tumors, and organ toxicity. To address these obstacles, PEGylated and non-PEGylated liposomes containing CTLA-4 was prepared and characterized and the anti-tumor therapeutic responses were studied on the mice bearing C26 colon cancer tumors. The biodistribution study showed that the PEGylated liposomes had prolonged blood half-lives and accumulated remarkably more than non-PEGylated liposomes and free CTLA-4 antibody in tumor area. The lowest tumor volumes, highest time to reach end points (TTE: 34.29±3.09 days) and tumor growth delay percent (TGD: 29.37%) were seen in mice that received PEGylated liposomes than free CTLA-4 blocking antibody treatment (TTE: 31.16±4.13 days, TGD: 17.57%). In conclusion, PEGylated liposomes containing anti CTLA-4 antibody are delivered to tumor sites more efficiently and have a greater effect on anti-tumor immune responses than free antibodies and merits further investigation.