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 (TSCM) cells is expected to overcome this shortcoming as TSCM 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 TSCM-like cells (iTSCM) by coculturing with OP9 cells expressing Notch ligand, Delta-like 1 (OP9-hDLL1). Here we show the methodological parameters of human CD8+ iTSCM cell generation and their application to adoptive cancer immunotherapy. Regardless of the stimulation by anti-CD3/CD28 antibodies or by antigen-presenting cells, human iTSCM cells were more efficiently induced from central memory type T cells than from effector memory T cells. During the induction phase by coculture with OP9-hDLL1 cells, interleukin (IL)-7 and IL-15 (but not IL-2 or IL-21) could efficiently generate iTSCM cells. Epstein–Barr virus-specific iTSCM 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 iTSCM offers a promising therapeutic strategy for cancer immunotherapy.
| Original language | English |
|---|---|
| Pages (from-to) | 2130-2140 |
| Number of pages | 11 |
| Journal | Cancer Science |
| Volume | 109 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2018 Jul 1 |
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Keywords
- adoptive immunotherapy
- cytokine
- Epstein–Barr virus
- immunological memory
- methodological study
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Generation and application of human induced-stem cell memory T cells for adoptive immunotherapy. / Kondo, Taisuke; Imura, Yuki; Chikuma, Shunsuke; Hibino, Sana; Omata-Mise, Setsuko; Ando, Makoto; Akanuma, Takashi; Iizuka, Mana; Sakai, Ryota; Morita, Rimpei; Yoshimura, Akihiko.
In: Cancer Science, Vol. 109, No. 7, 01.07.2018, p. 2130-2140.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Generation and application of human induced-stem cell memory T cells for adoptive immunotherapy
AU - Kondo, Taisuke
AU - Imura, Yuki
AU - Chikuma, Shunsuke
AU - Hibino, Sana
AU - Omata-Mise, Setsuko
AU - Ando, Makoto
AU - Akanuma, Takashi
AU - Iizuka, Mana
AU - Sakai, Ryota
AU - Morita, Rimpei
AU - Yoshimura, Akihiko
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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 (TSCM) cells is expected to overcome this shortcoming as TSCM 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 TSCM-like cells (iTSCM) by coculturing with OP9 cells expressing Notch ligand, Delta-like 1 (OP9-hDLL1). Here we show the methodological parameters of human CD8+ iTSCM cell generation and their application to adoptive cancer immunotherapy. Regardless of the stimulation by anti-CD3/CD28 antibodies or by antigen-presenting cells, human iTSCM cells were more efficiently induced from central memory type T cells than from effector memory T cells. During the induction phase by coculture with OP9-hDLL1 cells, interleukin (IL)-7 and IL-15 (but not IL-2 or IL-21) could efficiently generate iTSCM cells. Epstein–Barr virus-specific iTSCM 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 iTSCM offers a promising therapeutic strategy for cancer immunotherapy.
AB - 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 (TSCM) cells is expected to overcome this shortcoming as TSCM 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 TSCM-like cells (iTSCM) by coculturing with OP9 cells expressing Notch ligand, Delta-like 1 (OP9-hDLL1). Here we show the methodological parameters of human CD8+ iTSCM cell generation and their application to adoptive cancer immunotherapy. Regardless of the stimulation by anti-CD3/CD28 antibodies or by antigen-presenting cells, human iTSCM cells were more efficiently induced from central memory type T cells than from effector memory T cells. During the induction phase by coculture with OP9-hDLL1 cells, interleukin (IL)-7 and IL-15 (but not IL-2 or IL-21) could efficiently generate iTSCM cells. Epstein–Barr virus-specific iTSCM 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 iTSCM offers a promising therapeutic strategy for cancer immunotherapy.
KW - adoptive immunotherapy
KW - cytokine
KW - Epstein–Barr virus
KW - immunological memory
KW - methodological study
UR - http://www.scopus.com/inward/record.url?scp=85049337759&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049337759&partnerID=8YFLogxK
U2 - 10.1111/cas.13648
DO - 10.1111/cas.13648
M3 - Article
VL - 109
SP - 2130
EP - 2140
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 7
ER -