Journal
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
Volume 14, Issue 9, Pages 1645-1653Publisher
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2018.2619
Keywords
Hepatocellular Carcinoma; Bispecific T-Cell Engager; Aptamer/Antibody Bispecific System; Aptamer
Funding
- Programs for the Key Project of National Natural Science Foundation of China [81430055]
- Programs for Changjiang Scholars and Innovative Research Team in University [IRT_15R13]
- Guangxi Science and Technology Base and Talent Project [AD17129062]
- International Cooperation Project of the Ministry of Science and Technology of China [2015DFA31320]
- Project for Innovative Research Team in Guangxi Natural Science Foundation [2015GXNSFFA139001]
- Project of Science and Technology of Guangxi [14125008-2-12, 1599005-2-10]
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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-1carboxylate (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.
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