Enhancing the Anti-Hepatocarcinoma Efficacy of Cytokine Induced Killer Cells by TLS11a-Lipo-hENG scFv/hIP-10 Nanocapsules

Abstract

Developing a novel therapeutic approach to prevent and treat hepatocellular carcinoma (HCC) is essential. As an adoptive cell therapy candidate, cytokine-induced killer (CIK) cell immunotherapy is ideal. However, for efficacy in vivo delivery of CIK cells conjugate with antibody antineoplastic agents into the cancer cells, various biological obstacles including rapid degradation in vivo and the absence of active targeting capability need to be overcome. Previously, we developed a fusion antibody-chemokine protein which contained human Endoglin antibodies and human Interferon-gamma-induced protein 10 (hENG scFv/hIP-10). To this end, we present that a novel synthesized TLS11a-Lipo-hENG scFv/hIP-10 nanocapsules, which combine the advantages of prolonged half-life and good stability liposomes and HCC-specific targeting aptamer “TLS11a,” would be able to realize efficient and effective in vivo therapy. Also, we find that in combination with CIK cells possess a greater anti-hepatocarcinoma efficacy. Combined with TLS11a-Lipo-hENG scFv/hIP-10 nanocapsules and CIK cells, they could suppress tumor growth and prolong the survival of hepatoma-bearing mice through recruiting endogenous CIK cells in tumor tissues, inhibiting cell proliferation in tumors while promoting apoptosis and producing IFN-γ level. It appears that TLS11a-Lipo-hENG scFv/hIP-10 nanocapsules can enhance the antitumor activity of CIK cells against human hepatocellular carcinoma.