Adoptive immunotherapy using liver natural killer cells for preventing recurrence of hepatocellular carcinoma in cadaveric donor liver transplantation (53.20)

Abstract

Abstract Tumor recurrence is the limitation of liver transplant (LT) in patients with hepatocellular carcinoma (HCC). However, there is no prevention or treatment for HCC recurrence after LT. Here, we describe a clinical-scale method for an adoptive immunotherapy that uses natural killer (NK) cells derived from donor liver graft perfusate to prevent HCC recurrence after LT. Liver mononuclear cells (LMNC) that were extracted from the deceased donor liver graft perfusate contained a large percentage of NK cells (45.0% ± 4.0%) compared with peripheral blood mononuclear cells (PBMC) (21.8% ± 5.2%) from the same donor. Furthermore, interleukin (IL)-2-stimulated NK cells showed greater upregulation of activation markers and the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is critical for NK cell-mediated anti-tumor cell. Moreover, IL-2 stimulation induced LMNC to exhibit a stronger cytotoxicity against HCC compared with PBMC (p < 0.01). After obtaining approval from the FDA and IRB of our institute, we successfully applied this approach to 10 liver cirrhotic patients (9M / 1F) with HCC (Clinicaltrial.gov #NCT01147380). The average number of administered NK cells was 175 × 106 cells/body. After infusion, cytotoxicity, TRAIL, NKp44, and CD226 expression on NK cells significantly increased in patients’ PBMC (p < 0.05). There are no study related adverse events. In conclusion, the administration of IL-2-stimulated cadaveric donor liver NK cells is well tolerated.