Large-Scale Production and Characterization of Novel CD4+ Cytotoxic T Cells with Broad Tumor Specificity for Immunotherapy
Immune-cell–based approaches using cytotoxic and dendritic cells are under constant scrutiny to design novel therapies for the treatment of tumors. These strategies are hampered by the lack of efficient and economical large-scale production methods for effector cells. Here we describe the propagatio...
Saved in:
Published in | Molecular cancer research Vol. 7; no. 3; pp. 339 - 353 |
---|---|
Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Association for Cancer Research
01.03.2009
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Immune-cell–based approaches using cytotoxic and dendritic cells are under constant scrutiny to design novel therapies for
the treatment of tumors. These strategies are hampered by the lack of efficient and economical large-scale production methods
for effector cells. Here we describe the propagation of large amounts of a unique population of CD4 + cytotoxic T cells, which we termed tumor killer T cells (TKTC), because of their potent and broad antitumor cell activity.
With this cultivation strategy, TKTCs from peripheral blood mononuclear cells are generated within a short period of time
using a pulse with a stimulating cell line followed by continuous growth in serum-free medium supplemented with a mixture
of interleukin-2 and cyclosporin A. Expression and functional profiling did not allow a classification of TKTCs to any thus
far defined subtype of T cells. Cytotoxic assays showed that TKTCs kill a panel of tumor targets of diverse tissue origin
while leaving normal cells unaffected. Blocking experiments revealed that TKTC killing was, to a significant extent, mediated
by tumor necrosis factor-related apoptosis-inducing ligand and was independent of MHC restriction. These results suggest that
TKTCs have a high potential as a novel tool in the adoptive immunotherapy of cancer. (Mol Cancer Res 2009;7(3):339–53) |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1541-7786 1557-3125 |
DOI: | 10.1158/1541-7786.MCR-07-2208 |