Evren Alici

37 Pages·2016·6.05 MB·English

by  European Medicines Agency

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