Background: To explore the feasibility and safety of natural killer (NK) cell therapy in HCC, we performed a prospective, open-label, phase I trial to evaluate the synergistic effect of locoregional high-dose autologous NK cell therapy in combination with hepatic arterial infusion chemotherapy (HAIC).Methods: Patients with locally advanced HCC who were refractory to the standard treatment were eligible for this study. Patients received expanded and activated NK cells for 5 consecutive days in a dose-escalating manner (dose 2.5×10⁸, 5×10⁸, 10×10⁸ NK cells/injection) through hepatic arterial infusion following 4 cycles of HAIC with 5-fluorouracil (750 mg/m²) and cisplatin (25 mg/m²). The primary endpoint was the safety of NK cell-based immunotherapy, and the secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and immunologic responses.Results: Of the 11 patients enrolled, the confirmed ORR was 63.6% (complete response [CR]: 36.4%, confirmed partial response [PR]: 27.3%). Stable disease (SD) and progressive disease (PD) were observed in two patients (18.2%) each, resulting in a disease control rate (DCR) of 81.8%. The median PFS and OS were 10.3 and 41.6 months, respectively. There were no incidences of decompensation or severe adverse events during HAIC, and no adverse events related to NK cell infusion were noted.Conclusion: The combination of HAIC and locoregional high-dose NK cell therapy is a safe and effective treatment for locally advanced HCC patients who were refractory to the standard treatment. This result warrants further development of this novel treatment to establish its efficacy in HCC. Clinical Trial Registration: cris.nih.go.kr, identifier KCT0003973.

Lee YH, et al. Ann Hepatobiliary Pancreat Surg. 2018 Nov;22(4):335-343. https://doi.org/10.14701/ahbps.2018.22.4.335

Photothermal therapy (PTT) using a near-infrared (NIR) heptamethine cyanine fluorophore has emerged as an alternative strategy for targeted cancer therapy. NIR fluorophores showing a high molar extinction coefficient and low fluorescence quantum yield have considerable potential applications in photothermal cancer therapy. In this study, a bifunctional sorbitol–ZW800 conjugate was used as an advanced concept of photothermal therapeutic agents for in vivo cancer imaging and therapy owing to the high tumor targetability of the sorbitol moiety and excellent photothermal property of NIR heptamethine cyanine fluorophore. The sorbitol–ZW800 showed an excellent photothermal effect increased by 58.7 °C after NIR laser irradiation (1.1 W/cm²) for 5 min. The HT-29 tumors targeted by sorbitol–ZW800 showed a significant decrease in tumor volumes for 7 days after photothermal treatment. Therefore, combining the bifunctional sorbitol–ZW800 conjugate and NIR laser irradiation is an alternative way for targeted cancer therapy, and this approach holds great promise as a safe and highly efficient NIR photothermal agent for future clinical applications.

Song SH, et al. Ann Hepatobiliary Pancreat Surg. 2020 Feb;24(1):57-62. https://doi.org/10.14701/ahbps.2020.24.1.57