Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes.
Details
Serval ID
serval:BIB_48CB18315AF2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes.
Journal
Journal of Translational Medicine
ISSN
1479-5876 (Electronic)
ISSN-L
1479-5876
Publication state
Published
Issued date
2011
Volume
9
Pages
131
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: epublish
Abstract
BACKGROUND: Development of a standardized platform for the rapid expansion of tumor-infiltrating lymphocytes (TILs) with anti-tumor function from patients with limited TIL numbers or tumor tissues challenges their clinical application.
METHODS: To facilitate adoptive immunotherapy, we applied genetically-engineered K562 cell-based artificial antigen presenting cells (aAPCs) for the direct and rapid expansion of TILs isolated from primary cancer specimens.
RESULTS: TILs outgrown in IL-2 undergo rapid, CD28-independent expansion in response to aAPC stimulation that requires provision of exogenous IL-2 cytokine support. aAPCs induce numerical expansion of TILs that is statistically similar to an established rapid expansion method at a 100-fold lower feeder cell to TIL ratio, and greater than those achievable using anti-CD3/CD28 activation beads or extended IL-2 culture. aAPC-expanded TILs undergo numerical expansion of tumor antigen-specific cells, remain amenable to secondary aAPC-based expansion, and have low CD4/CD8 ratios and FOXP3+ CD4+ cell frequencies. TILs can also be expanded directly from fresh enzyme-digested tumor specimens when pulsed with aAPCs. These "young" TILs are tumor-reactive, positively skewed in CD8+ lymphocyte composition, CD28 and CD27 expression, and contain fewer FOXP3+ T cells compared to parallel IL-2 cultures.
CONCLUSION: Genetically-enhanced aAPCs represent a standardized, "off-the-shelf" platform for the direct ex vivo expansion of TILs of suitable number, phenotype and function for use in adoptive immunotherapy.
METHODS: To facilitate adoptive immunotherapy, we applied genetically-engineered K562 cell-based artificial antigen presenting cells (aAPCs) for the direct and rapid expansion of TILs isolated from primary cancer specimens.
RESULTS: TILs outgrown in IL-2 undergo rapid, CD28-independent expansion in response to aAPC stimulation that requires provision of exogenous IL-2 cytokine support. aAPCs induce numerical expansion of TILs that is statistically similar to an established rapid expansion method at a 100-fold lower feeder cell to TIL ratio, and greater than those achievable using anti-CD3/CD28 activation beads or extended IL-2 culture. aAPC-expanded TILs undergo numerical expansion of tumor antigen-specific cells, remain amenable to secondary aAPC-based expansion, and have low CD4/CD8 ratios and FOXP3+ CD4+ cell frequencies. TILs can also be expanded directly from fresh enzyme-digested tumor specimens when pulsed with aAPCs. These "young" TILs are tumor-reactive, positively skewed in CD8+ lymphocyte composition, CD28 and CD27 expression, and contain fewer FOXP3+ T cells compared to parallel IL-2 cultures.
CONCLUSION: Genetically-enhanced aAPCs represent a standardized, "off-the-shelf" platform for the direct ex vivo expansion of TILs of suitable number, phenotype and function for use in adoptive immunotherapy.
Keywords
Antigen-Presenting Cells/cytology, Antigen-Presenting Cells/drug effects, Antigens, CD28/metabolism, Antigens, Neoplasm/immunology, Artificial Cells/cytology, Artificial Cells/drug effects, Cell Culture Techniques/methods, Cell Proliferation/drug effects, Epitopes/immunology, Genetic Engineering, Humans, Interleukin-2/pharmacology, Lymphocyte Subsets/drug effects, Lymphocyte Subsets/immunology, Lymphocytes, Tumor-Infiltrating/cytology, Lymphocytes, Tumor-Infiltrating/drug effects, Phenotype
Pubmed
Web of science
Open Access
Yes
Create date
14/10/2014 11:43
Last modification date
20/08/2019 13:55