Premium
Multivariate statistical data analysis as a tool to analyze ex vivo expansion dynamics of cytokine‐induced killer cells
Author(s) -
Za Cristina,
Stocchero Matteo,
Albiero Elena,
Castegnaro Silvia,
Chieregato Katia,
Madeo Domenico,
Rodeghiero Francesco,
Astori Giuseppe
Publication year - 2014
Publication title -
cytometry part b: clinical cytometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.646
H-Index - 61
eISSN - 1552-4957
pISSN - 1552-4949
DOI - 10.1002/cyto.b.21124
Subject(s) - cytokine induced killer cell , cd3 , cd8 , cytotoxic t cell , cytokine , multivariate statistics , immunology , immunotherapy , biology , immune system , statistics , mathematics , in vitro , biochemistry
Background Cytokine‐induced killer (CIK) cells, obtained after mononucleated cell stimulation with interferon‐γ, interleukin‐2, and anti‐CD3 antibody, are constituted by CD3 + CD56 + (CIK) cells and a minority of natural killer (NK; CD3 − CD56 + ) cells and T‐lymphocytes (CD3 + CD56 − ) with antitumor effect against hematological malignancies, thus representing a promising immunotherapy strategy. To ensure in vivo antitumor activity it is mandatory to maximize the percentage of CD3 + 56 + effector cells, which is highly variable depending on the starting sample and the harvesting day. Based on cytofluorimetric data, we have retrospectively applied multivariate statistical data analysis (MVDA) to 30 expansions building mathematical models able to predict the expansion fate and the optimal CIK harvesting day. Methods Cell phenotype was monitored during culture; multivariate batch statistical process control was applied to monitor cell expansion and orthogonal projections to latent structures to predict CIK percentage. Results Ten expansions had CD3 + CD56 + cells ≥40% (good batches) and 20 had CD3 + CD56 + cells ≤40%. In 36.7%, CD3 + CD56 + cells reached the highest concentration at day 17 and the others at day 21. We built a highly predictive regression model for estimating CD3 + CD56 + cells during culture. Three variables resulted highly informative: NK % at day 0, cytotoxic T‐lymphocytes % (CTLs, CD3 + CD8 + ) at day 4, and CIK % at day 7. “Good batches” are characterized by a high percentage of CTLs and CD3 + CD56 + cells at day 4 and day 7, respectively. Conclusion By applying MVDA it is possible to optimize CIK expansion, deciding the optimal cell harvesting day. A predictive role for CTL and CIK was evidenced. © 2013 International Clinical Cytometry Society