Roman M. Shapiro, Michal Sheffer, Matthew A. Booker, Michael Y. Tolstorukov, Grace C. Birch, Moshe Sade-Feldman, Jacy Fang, Shuqiang Li, Wesley Lu, Michela Ansuinelli, Remy Dulery, Mubin Tarannum, Joanna Baginska, Nishant Dwivedi, Ashish Kothari, Livius Penter, Yasmin Z. Abdulhamid, Isabel E. Kaplan, Dinh Khanhlinh, Ravindra Uppaluri, Robert A. Redd, Sarah Nikiforow, John Koreth, Jerome Ritz, Catherine J. Wu, Robert J. Soiffer, glenn hanna, Rizwan Romee
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引用次数: 0
Abstract
Cytokine induced memory-like natural killer (CIML NK) cells combined with an IL-15 super-agonist (N-803) are a novel modality to treat relapsed/refractory head and neck cancer. We report data from a phase I trial of haploidentical CIML NK cells combined with N-803 with or without ipilimumab (IPI) in relapsed/refractory head and neck cancer patients after a median of 6 prior lines of therapy. The primary endpoint was safety, which was established, with dose-limiting toxicity in 1/10 patients. A promising though transient disease control rate of 70% correlated with donor NK cell expansion, the latter occurring irrespective of IPI. High-resolution immunophenotypic and transcriptional profiling characterized the NK cells and their interacting partners in vivo. IPI was associated with contraction of Treg:Tcon, rapid recovery of recipient CD8+ T cells, and accelerated rejection of donor NK cells. These results inform evaluation of CIML NK therapy for advanced malignancies, with considerations for combination with IPI.
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