ABSTRACT
NK cell adoptive therapy is a promising cancer therapeutic approach, but there are significant challenges that limiting its feasibility and clinical efficacy. One difficulty is the paucity of clinical grade manufacturing platforms to support the large scale expansion of highly active NK cells. We created an NK cell feeder cell line termed 'NKF' through overexpressing membrane bound IL-21 that is capable of inducing robust and sustained proliferation (>10,000-fold expansion at 5 weeks) of highly cytotoxic NK cells. The expanded NK cells exhibit increased cytotoxic function against a panel of blood cancer and solid tumor cells as compared to IL-2-activated non-expanded NK cells. The NKF-expanded NK cells also demonstrate efficacy in mouse models of human sarcoma and T cell leukemia. Mechanistic studies revealed that membrane-bound IL-21 leads to an activation of a STAT3/c-Myc pathway and increased NK cell metabolism with a shift towards aerobic glycolysis. The NKF feeder cell line is a promising new platform that enables the large scale proliferation of highly active NK cells in support of large scale third party NK cell clinical studies that have been recently intiatied. These results also provide mechanistic insights into how membrane-bound IL-21 regulates NK cell expansion.
Subject(s)
Feeder Cells/metabolism , Immunotherapy/methods , Killer Cells, Natural/immunology , Neoplasms/therapy , Primary Cell Culture/methods , Animals , Cell Line, Tumor , Cell Membrane/immunology , Cell Membrane/metabolism , Cell Proliferation , Coculture Techniques , Healthy Volunteers , Humans , Interleukins/immunology , Interleukins/metabolism , Killer Cells, Natural/metabolism , Killer Cells, Natural/transplantation , Mice , Neoplasms/immunology , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: Allergic contact dermatitis is an inflammatory condition that less commonly presents with scalp involvement. Recently, T regulatory cells have been documented to be residents of hair follicles, illuminating why contact allergens are less likely to elicit dermatitis in the scalp. OBJECTIVE: The aims of the study were to determine the prevalence of scalp symptoms, with and without other affected areas, in patients presenting for evaluation of allergic contact dermatitis and to determine the allergens most likely to be associated with scalp dermatitis. METHODS: We examined allergens commonly found in hair products and stratified positive patch test results by the following affected areas: face, eyelid, neck, or hands, where exposure by runoff is common, versus scalp. CONCLUSIONS: Para-phenylenediamine (PPD) is the most common allergen in patients with scalp dermatitis. The rate of PPD sensitization is higher in nonwhite compared with white patients. In the small number of patients with isolated scalp involvement, positive patch tests to PPD were documented in a minority. Other allergens found in hair products may present without scalp symptoms. Patients with dermatitis affecting areas other than the scalp should provide their hair product ingredients to guide patch test selection.
