A phagocytic cell line markedly improves survival of infected neutropenic mice

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Abstract
Disseminated candidiasis is a frequent infection in neutropenic patients, in whom it causes 50% mortality, despite antifungal therapy. As the duration of neutropenia is the strongest predictor of survival in neutropenic patients with invasive fungal infections, neutrophil transfusions are a logical, therapeutic option. However, significant technical barriers have prevented the clinical use of neutrophil transfusions. To overcome these barriers, we identified a human phagocytic cell line that could be administered to candidemic hosts in lieu of freshly harvested neutrophils. HL‐60 cells killed Candida albicans in vitro. Activation of HL‐60 cells with dimethyl sulfoxide and retinoic acid abrogated the cells’ proliferation and augmented their killing of C. albicans. Administration of activated HL‐60 cells to candidemic, neutropenic mice significantly improved survival (53% vs. 0%). Live HL‐60 cells chemotaxed to sites of infection, phagocytized C. albicans, and reduced the fungal burden in key target organs. Although unactivated HL‐60 cells also reduced tissue fungal burden in vivo, they did not improve survival as a result of their toxicity in infected mice. In contrast, no toxicity as a result of activated HL‐60 cells was observed at up to 2 months of follow‐up. To our knowledge, this is the first description of a cell line‐based immunotherapy for an infectious disease. With further refinements, activated HL‐60 cells have the potential to overcome the technical barriers to neutrophil transfusions.
Funding Information
  • National Institute of Allergy and Infectious Diseases (RO3 AI054531, RO1 AI19990, KO8 AI060641)
  • Infectious Diseases from Bristol Myers Squibb