Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy

Kondo, Taisuke; Morita, Rimpei; Okuzono, Yuumi; Nakatsukasa, Hiroko; Sekiya, Takashi; Chikuma, Shunsuke; Shichita, Takashi; Kanamori, Mitsuhiro; Kubo, Masato; Koga, Katsumi; Miyazaki, Takahiro; Kassai, Yoshiaki; Yoshimura, Akihiko

doi:10.1038/ncomms15338

Cited by 88 publications

(88 citation statements)

References 39 publications

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“…Stem cell memory T cells expressed naïve T‐cell surface markers, CD44 low CD62L high CCR7 + in mice and CD45RA + CD45RO − CCR7 + CD62L + in humans . These cells possess high proliferative and long‐term survival abilities in vivo, producing a large number of effector T cells with potent antitumor functions . Similar naïve‐like memory T cells were discovered in human and called memory T cells with a naive phenotype .…”

Section: Introductionmentioning

confidence: 89%

“…[16][17][18][19][20] We have established a novel two-step culture system for T SCM induction, which is constituted by a "prime" step and an "induction" step, and have named the induced-T SCM "induced-T SCM (iT SCM )" cells. 12 In this paper, we describe a detailed methodology of iT SCM generation and report optimal conditions of priming and cytokine treatment. We also investigate the antitumor efficacy of human iT SCM cells in a humanized mouse model.…”

Section: Memory T Cells Have Been Classified Into Two Subpopulationsmentioning

confidence: 99%

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Generation and application of human induced‐stem cell memory T cells for adoptive immunotherapy

et al. 2018

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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.

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Section: Introductionmentioning

confidence: 89%

Section: Memory T Cells Have Been Classified Into Two Subpopulationsmentioning

confidence: 99%

Generation and application of human induced‐stem cell memory T cells for adoptive immunotherapy

et al. 2018

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“…The number of memory T cells required for initial adoptive transfer therapy will be significantly lower than the current practice as memory cells can be primed in vivo using vaccine to regenerate CTL as needed. Current approaches to induce Tscm-like ACT include 1) Cytokines addition: IL-7, IL-15, IL-21 [70]; 2) using inhibitors for AKT,m-TORC and PI3K [71,72]; 3) activation of NOTCH [73]; 4) Weak TCR signaling during activation [74]; 5)providing additional costimulation e.g. 4-1BB, ICOS [75]; 6) altered metabolism status [76,77].…”

Section: The Influence Of Immunosuppressive Tumor Microenvironment (Tmentioning

confidence: 99%

Adoptive CD8+ T cell therapy against cancer:Challenges and opportunities

Jiang

Liu

et al. 2019

Cancer Letters

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“…A recent study indicated that Notch signaling redirects differentiation from memory precursor-like activated CD8 + T cells to stem cell memory T-like cells, which have a long-lived and self-renewing potential [75]. Interestingly, miRNAs, such as miR-34, miR-598 and miR-433, regulate cancer stem cells by targeting the molecules of the Notch signaling pathway [76][77][78].…”

Section: Mirna Regulation Of Signaling Pathwaysmentioning

confidence: 99%

Regulation of Memory CD8+ T Cell Differentiation by MicroRNAs

Zhang

et al. 2018

Cell Physiol Biochem

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MicroRNAs (miRNAs) have emerged as crucial regulators of T lymphocyte survival, differentiation and function, all of which are key factors impacting the outcome of adoptive T cell-based immunotherapy. It has become increasingly clear that the adoptive transfer of memory CD8⁺ T cell subsets is highly correlated with objective clinical responses for patients with advanced cancer. However, it is unclear how to improve the long-term persistence of transferred CD8⁺ T cells using miRNAs. Here, we highlight the current advances in our understanding of the role of miRNAs in regulating the differentiation of memory CD8⁺ T cells. We specifically discuss the effect of miRNAs on key transcription factors, immune checkpoints and signal pathways, which contribute to the differentiation of effector and memory T cell subsets. Ultimately, miRNAs may be easily integrated into existing T cell receptor (TCR) and chimeric antigen receptor (CAR) platforms to promote adoptive T cell therapy with multiple advantages. Thus, combining T cell-based therapy with miRNAs could be considered a promising and robust strategy for cancer treatment.

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Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy

Cited by 88 publications

References 39 publications

Generation and application of human induced‐stem cell memory T cells for adoptive immunotherapy

Generation and application of human induced‐stem cell memory T cells for adoptive immunotherapy

Adoptive CD8+ T cell therapy against cancer:Challenges and opportunities

Regulation of Memory CD8+ T Cell Differentiation by MicroRNAs

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