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
Title
Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes.
Journal
Journal of Translational Medicine
Author(s)
Ye Q., Loisiou M., Levine B.L., Suhoski M.M., Riley J.L., June C.H., Coukos G., Powell D.J.
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.
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
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