University of Minnesota

The University of North Carolina at Chapel Hill

St. Jude Children's Research Hospital

Albert-ludwigs-universitat Freiburg

Mallinckrodt Pharmaceuticals Ireland Limited

Albert-ludwigs-universitaet Freiburg

Robert Zeiser

Bruce Robert Blazar

Jeff S Miller

Brent Koehn

Peter J Murray

Jenny P Y Ting

Justus Duyster

Petya Apostolova

Brent H Koehn

The present invention relates to a method comprising the steps of provision of a sample derived from a blood sample of a subject that has received a checkpoint-inhibitor therapy and is suspected of developing or has developed symptoms of immune-related adverse events (irAE), adding a photosensitizing agent to the sample, and subjecting the sample to irradiation, which preferably generates immunoregulatory NK cells in said sample. In embodiments, the photosensitizing agent is 8-methoxypsoralen and/or the irradiation is UVA irradiation. In another aspect, the invention relates to immunoregulatory NK cells obtained from a method comprising the steps of provision of a sample derived from an isolated blood sample of a subject, adding a photosensitizing agent to the sample, and subjecting the sample to irradiation. Furthermore, the invention encompasses immunoregulatory NK cells for use in the treatment and/or prevention of irAE in a subject that has received a checkpoint-inhibitor therapy.

Method for generating immunoregulatory cells in a blood-derived sample

In one aspect, a method of treating a subject having or at risk of having graft-versus-host disease (GvHD) generally includes administering to the subject a plurality of myeloid-derived suppressor cells (MDSCs) effective to ameliorate at least one symptom or clinical sign of graft-versus-host disease compared to a suitable control subject. In another aspect, a method of treating a tumor in a subject generally includes administering to the subject an anti-tumor therapy and co-administering to the subject an inflammasome inciting agent in an amount effective to increase inflammasome activation of MDSCs sufficiently to reduce suppressor function of the MDSCs.

Therapeutic methods involving modulating inflammasome activation of myeloid-derived suppressor cells

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Freiburg, Germany

Robert Zeiser