Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy
Lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells boosts antitumor immunotherapeutic activity in mouse and in humans. In the most recent clinical trials, lymphodepletion together with ACT has an objective response rate of 50% in patients with solid metast...
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Published in | Trends in immunology Vol. 26; no. 2; pp. 111 - 117 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier Ltd
01.02.2005
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Subjects | |
Online Access | Get full text |
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Summary: | Lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells boosts antitumor immunotherapeutic activity in mouse and in humans. In the most recent clinical trials, lymphodepletion together with ACT has an objective response rate of 50% in patients with solid metastatic tumors. The mechanisms underlying this recent advance in cancer immunotherapy are beginning to be elucidated and include: the elimination of cellular cytokine ‘sinks’ for homeostatic γ
C-cytokines, such as interleukin-7 (IL-7), IL-15 and possibly IL-21, which activate and expand tumor-reactive T cells; the impairment of CD4
+CD25
+ regulatory T (Treg) cells that suppress tumor-reactive T cells; and the induction of tumor apoptosis and necrosis in conjunction with antigen-presenting cell activation. Knowledge of these factors could be exploited therapeutically to improve the
in vivo function of adoptively transferred, tumor-reactive T cells for the treatment of cancer. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Feature-3 ObjectType-Review-1 Written in partial fulfillment of a PhD in Biochemistry at the George Washington University, Washington, DC 20052, USA. |
ISSN: | 1471-4906 1471-4981 |
DOI: | 10.1016/j.it.2004.12.003 |