Prolonged recurrence-free survival by autologous rectronectin-activated killer (RAK) cells in resected high-risk hepatocellular carcinoma: an experimental single-arm phase II trial (pilot study)

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.