自体 rectronectin 激活杀伤（RAK）细胞在切除后高危肝细胞癌中延长无复发生存期：一项实验性单臂 II 期试验（初步研究）

Hepatocellular carcinoma (HCC) is prone to recurrence following hepatectomy, posing significant clinical challenges. Our previous research suggested that adoptive T-cell therapy could improve the impaired liver microenvironment. This study aimed to evaluate the efficacy and safety of adjuvant RetroNectin-Activated Killer (RAK) cell therapy to prevent the recurrence of HCC post-hepatectomy in high-risk patients and explore potential mechanisms.

This was a single-center, single-arm, open-label, experimental phase II trial. Following surgical resection, HCC patients with high-risk factors for recurrence received quarterly intravenous injections of RAK cells (1 × 10 10 cells every cycle) over three cycles. The primary endpoints were recurrence-free survival (RFS) and safety, with overall survival as the secondary endpoint. Exploratory studies were conducted on paired blood serum and tumor biopsy samples.

Of the 27 patients recruited, 22 received infusions, and 19 with confirmed R0 resection were included in the survival analysis. With a median follow-up of 51 months, the 1-year and 3-year RFS rates were 79% (15/19) and 68% (13/19), respectively. Compared to matched controls, data indicated prolonged RFS (median RFS not reached vs. 13.2 months, hazard ratio 0.31, 95% CI 0.12-0.81; P = 0.017). No significant treatment-related adverse events were reported, further confirmed by analyzing 120 serum cytokines. Lymphocyte surveillance identified in vivo expansion of CD8 + T cells. Tumors from early recurrent patients featured upregulated ECM-related pathways and elevated IL-11 levels. Imaging mass cytometry revealed the maintained quantity and functionality of CD8 + T cells post-treatment.

The efficacy of autologous RAK cell therapy as a viable adjuvant therapy for preventing recurrence in patients with high-risk HCC is promising, both from clinical outcomes and underlying mechanisms.