TLS11a Aptamer/CD3 Antibody Anti-Tumor System for Liver Cancer

J Biomed Nanotechnol. 2018 Sep 1;14(9):1645-1653. doi: 10.1166/jbn.2018.2619.

Abstract

New therapeutic approaches are needed for hepatocellular carcinoma (HCC), which is the most common primary malignancy of the liver. Bispecific T-cell engagers (BiTE) can effectively redirect T cells against tumors and show a strong anti-tumor effect. However, the potential immunogenicity, complexity, and high cost significantly limit their clinical application. In this paper, we used the hepatoma cells-specific aptamer TLS11a and anti-CD3 for to establish an aptamer/antibody bispecific system (AAbs), TLS11a/CD3, which showed advantages over BiTE and can specifically redirect T cells to lyse tumor cells. TLS11a-SH and anti-CD3-NH2 were crosslinked with sulfosuccinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo-SMCC). T cell activation, proliferation, and cytotoxicity of TLS11a/CD3 were analyzed by flow cytometry. Cytokine array was used to detect cytokine released from activated T cells. Hepatoma xenograft model was used to monitor the tumor volume and survival. TLS11a/CD3 could specifically bind hepatoma cells (H22) and T cells, activated T cells to mediate antigen-specific lysis of H22 cells in vitro, and effectively inhibited the growth of implanted H22 tumors as well as prolonged mice survival. TLS11a/CD3 could simultaneously target hepatoma cells and T cells, specifically guide T cells to kill tumor cells, and enhance the anti-tumor effect of T cells both in vitro and in vivo.

MeSH terms

  • Animals
  • Antibodies, Bispecific
  • CD3 Complex
  • Carcinoma, Hepatocellular*
  • Humans
  • Liver Neoplasms*
  • Lymphocyte Activation
  • Mice

Substances

  • Antibodies, Bispecific
  • CD3 Complex