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

Nanomedicine. 2017 Nov;13(8):2671-2682. doi: 10.1016/j.nano.2017.08.010. Epub 2017 Aug 25.

Abstract

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.

Keywords: Antibodies; CTLA 4 antigen; Cancer; Immunotherapy; Liposomes.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • CTLA-4 Antigen / antagonists & inhibitors*
  • CTLA-4 Antigen / immunology
  • Cell Line, Tumor
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Female
  • Immunotherapy / methods
  • Liposomes / chemistry
  • Mice, Inbred BALB C
  • Polyethylene Glycols / chemistry

Substances

  • Antibodies, Monoclonal
  • CTLA-4 Antigen
  • Liposomes
  • Polyethylene Glycols