In:
Cancer Science, Wiley, Vol. 109, No. 7 ( 2018-07), p. 2130-2140
Abstract:
Adoptive T‐cell therapy is an effective strategy for cancer immunotherapy. However, infused T cells frequently become functionally exhausted, and consequently offer a poor prognosis after transplantation into patients. Adoptive transfer of tumor antigen‐specific stem cell memory T ( T SCM ) cells is expected to overcome this shortcoming as T SCM cells are close to naïve T cells, but are also highly proliferative, long‐lived, and produce a large number of effector T cells in response to antigen stimulation. We previously reported that activated effector T cells can be converted into T SCM ‐like cells ( iT SCM ) by coculturing with OP 9 cells expressing Notch ligand, Delta‐like 1 ( OP 9‐ hDLL 1). Here we show the methodological parameters of human CD 8 + iT SCM cell generation and their application to adoptive cancer immunotherapy. Regardless of the stimulation by anti‐ CD 3/ CD 28 antibodies or by antigen‐presenting cells, human iT SCM cells were more efficiently induced from central memory type T cells than from effector memory T cells. During the induction phase by coculture with OP 9‐ hDLL 1 cells, interleukin ( IL )‐7 and IL ‐15 (but not IL ‐2 or IL ‐21) could efficiently generate iT SCM cells. Epstein–Barr virus‐specific iT SCM cells showed much stronger antitumor potentials than conventionally activated T cells in humanized Epstein–Barr virus transformed‐tumor model mice. Thus, adoptive T‐cell therapy with iT SCM offers a promising therapeutic strategy for cancer immunotherapy.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2018.109.issue-7
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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