NK Cells Evren Alici, MD, PhD Karolinska Institutet, Department of Medicine, Division of Hematology Visiting Research Professor, Nova Southeastern University, FL, USA © Erik G Svensson 25/11/2016 Name Surname 1 Natural Killer cells Natural Killer Cells 3 What really goes on 4 NK cell abnormalities Abnormality Disease Decreased cytotoxic activity of NK cells NSC lung Ca Cervical Ca HCC Ovarian Ca CRC AML H&N Ca ALL Breast Ca B-CLL Squamous cell Ca CML Bronchogenic Ca MM Defective expression of activating receptors HCC AML M. melanoma MM Defective NK cell proliferation Renal Ca Nasopharyngeal Ca Neuroblastoma CML Increased number of CD56bright NK cells H&N Ca Breast Ca Defective expression of signalling molecules Cervical Ca Prostate Ca CRC AML Ovarian Ca CML Decreased NK cell counts Nasopharyngeal Ca CML Neuroblastoma ALL (Pediatric) Defective cytokine production AML CML ALL NK cell therapy overview Sutlu & Alici, JIM 2009 The expansion process Day 0 Detailed phenotypic characterization of NK cells CellGro SCGM Degranulation and cytotoxicity assays 5% Human AB serum IL-2 (500 U/ml) Day 0 Day 5 Day 10 Day 15 Day 20 13.6 1.48 15.6 2.91 39.6 14.7 53.7 19.7 72.4 6.58 OKT3 (10 ng/ml) 6 5 D C 18.2 66.7 17.4 64.1 2.36 43.3 0.39 26.2 1.37 19.6 CD3 Day 20 Every 2-3 days Additional medium with IL-2, without OKT3 cGMP certified expansion process A phase-I clinical trial with expanded NK cells Patient follow-up
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