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Patients with high-risk pediatric solid tumors experience poor outcomes and require improved treatments. NK cell immunotherapies hold promise for potential anti-tumor activity; however, clinical translation faces challenges.
In this single-institution Phase I trial (NCT01875601), we enrolled children and young adults with refractory solid tumors, to evaluate the manufacturing feasibility and safety of infusing activated NK cells. Using a 3+3 dose escalation design, NK cells were administered after lymphodepleting cyclophosphamide. Artificial antigen-presenting cells (aAPC) expressing human 4-1BBL and human IL-15RŒ± were used to expand autologous NK cells ex vivo. Three dose levels (DL) of NK cells were explored for Cohort A. Cohort B evaluated administration of NK cells followed by a ten-day rhIL-15 infusion.
Sixteen patients enrolled, with a median age of 16.1 years. The average ex vivo NK cell expansion was 19.4 fold. Expansion was insufficient to achieve the top DL. Following administration, partial responses per RECIST criteria were observed in 3 patients, two in DL1 of Cohort A, and one in DL1 of Cohort B. The remaining 13 patients had stable disease.
Symptoms of cytokine release syndrome occurred in 2/12 patients in Cohort A, one being a dose limiting toxicity. Four patients received rhIL-15 with one dose limiting toxicity related to pericardial tamponade and capillary leak syndrome, prior to pause of enrollment for supply issues.
Harvesting, expanding, and administering 1x107 cells/kg of aAPC-activated autologous NK cells is feasible and safe. Anti-tumor activity was observed following administration of aAPC-activated autologous NK cells with three partial responses. Correlative studies are underway.
Scientific Focus Area: Clinical Research
This page was last updated on Monday, September 25, 2023