Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial

Abstract

Renal cell cancer and malignant melanoma are two types of cancer that are responsive to immunotherapy. In this phase I dose-escalation study, the feasibility of large-scale expansion and safety of administering ex vivo-expanded NK-92 cells as allogeneic cellular immunotherapy in patients with refractory renal cell cancer and melanoma were determined. Twelve patients (aged 31–74 years) were enrolled, three per cohort at cell dose levels of 1 × 10⁸/m², 3 × 10⁸/m², 1 × 10⁹/m² and 3 × 10⁹/m². One treatment course consisted of three infusions. Eleven patients had refractory metastatic renal cell cancer; one patient had refractory metastatic melanoma. The NK-92 cells were expanded in X-Vivo 10 serum-free media supplemented with 500 U/mL Proleukin recombinant human interleukin-2 (rhIL-2), amino acids and 2.5% human AB plasma. Final yields of approximately 1 × 10⁹ cells/culture bag (218–250×expansion) over 15–17 days were achievable with ≥80% viability. Infusional toxicities of NK-92 were generally mild, with only one grade 3 fever and one grade 4 hypoglycemic episode. All toxicities were transient, resolved and did not require discontinuation of treatment. One patient was alive with disease at 4 years post-NK-92 infusion. The one metastatic melanoma patient had a minor response during the study period. One other patient exhibited a mixed response. This study establishes the feasibility of large-scale expansion and safety of administering NK-92 cells as allogeneic cellular immunotherapy in advanced cancer patients and serves as a platform for future study of this novel natural killer (NK)-cell based therapy.