Evaluation of Malarial Var2CSA-Displaying Baculovirus Vector in Transduction Efficiency in Human Cancer Cells

Biol Pharm Bull. 2023;46(3):404-411. doi: 10.1248/bpb.b22-00630.

Abstract

Baculovirus vectors (BVs) are able to use for gene transduction in mammalian cells and are recognized as growing viral vectors for cancer gene therapy applications. The transduction efficiency of BVs varies among cancer cell types. To improve the transduction efficiency of BVs in human cancer cells, BV displaying malarial variant surface antigen 2-chondroitin sulfate A (var2CSA) molecules was developed in this study. Var2CSA plays a critical role in the sequestration of Plasmodium falciparum-infected erythrocytes in the placenta. Moreover, var2CSA binds to cancer cells via placenta-like chondroitin sulfate A (CSA), but not to non-cancer cells. Var2CSA BV showed significantly higher gene transduction than control BV in HepG2 and Huh7 cells, human hepatic cancer cells as well as AsPC-1 cells, human pancreatic cancer cells. The transduction efficiency of var2CSA BV was significantly inhibited by the anti-gp64 antibody, free heparin, and CSA. The results of this study suggest that var2CSA BV would be an improved vector for cancer gene therapies, especially in the treatment of hepatic and pancreatic cancers.

Keywords: baculovirus vector; cancer gene therapy; transduction; variant surface antigen 2-chondroitin sulfate A (var2CSA).

MeSH terms

  • Animals
  • Antigens, Surface
  • Baculoviridae
  • Cell Line, Tumor
  • Chondroitin Sulfates
  • Female
  • Genetic Vectors
  • Humans
  • Liver Neoplasms*
  • Malaria*
  • Pancreatic Neoplasms*
  • Pregnancy
  • Transduction, Genetic

Substances

  • Antigens, Surface
  • Chondroitin Sulfates