Fate and function of anti-CD3/CD28-activated T cells following adoptive transfer: IL-2 promotes development of anti-tumor memory T cells in vivo

Hughes, Dennis P.M.; Baskar, D.; Urban, F. A.; Friedman, Michael S.; Braun, Thomas; McDonagh, Kevin T.

doi:10.1080/14653240500319127

Cited by 9 publications

(7 citation statements)

References 59 publications

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“… 33 , 41 There was an increased expression of T-bet in the Tc0 subset compared to the Tc17 subset, which we hypothesize is due to the natural tendency of CD8 + T cells to differentiate towards an inflammatory effector phenotype upon the addition of IL-2, anti-CD3, and anti-CD28 antibodies. 50 Indeed, we found that the addition of anti-IFN-γ to the Tc0 conditions induced a great reduction in the T-bet expression, strengthening this hypothesis. However, upon adoptive transfer, Tc0 cells up-regulated their expression of T-bet and IFN-γ production, indicating a switch towards the Tc1 phenotype.…”

Section: Discussionsupporting

confidence: 59%

Tc17 CD8+ T cells accumulate in murine atherosclerotic lesions, but do not contribute to early atherosclerosis development

Duijn

Jong

Benne

et al. 2020

Cardiovascular Research

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Aims CD8+ T-cells can differentiate into subpopulations that are characterized by a specific cytokine profile, such as the Tc17 population that produces IL-17. The role of this CD8+ T-cell subset in atherosclerosis remains elusive. In this study, we therefore investigated the contribution of Tc17 cells to the development of atherosclerosis. Methods and Results Flow cytometry analysis of atherosclerotic lesions from apoE-/- mice revealed a pronounced increase in RORγt+CD8+ T-cells compared to the spleen, indicating a lesion-specific increase in Tc17 cells. To study whether and how the Tc17 subset affects atherosclerosis, we performed an adoptive transfer of Tc17 cells or undifferentiated Tc0 cells into CD8-/-LDLr-/- mice fed a Western-type diet. Using flow cytometry, we showed that Tc17 cells retained a high level of IL-17A production in vivo. Moreover, Tc17 cells produced lower levels of IFN-γ than their Tc0 counterparts. Analysis of the aortic root revealed that the transfer of Tc17 cells did not increase atherosclerotic lesion size, in contrast to Tc0-treated mice. Conclusion These findings demonstrate a lesion-localized increase in Tc17 cells in an atherosclerotic mouse model. Tc17 cells appeared to be non-atherogenic, in contrast to their Tc0 counterpart. Translational perspective CD8+ T-cells are present in high numbers in human atherosclerotic plaques, however their role in inflammation and the pathogenesis of atherosclerosis remains elusive. Our results indicate that the majority of CD8+ T-cells in atherosclerotic plaques of mice have lost their ability to produce the pro-inflammatory cytokine IFN-γ and gain traits of IL-17-producing CD8+ T-cells (Tc17 cells). We show that this subset of CD8+ T-cells is less atherogenic then IFN-γ producing Tc1 cells.

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Section: Discussionsupporting

confidence: 59%

Tc17 CD8+ T cells accumulate in murine atherosclerotic lesions, but do not contribute to early atherosclerosis development

Duijn

Jong

Benne

et al. 2020

Cardiovascular Research

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“…IL-2 is able to influence several types of cancer effectively, including renal cell carcinoma, melanoma and liver cancer (7)(8)(9). In addition, recombination of the IL-2 gene has been clinically used as a type of drug to treat a variety of tumors (10,11).…”

Section: Introductionmentioning

confidence: 99%

Construction of the plasmid coding for the expression of the EGFP-M-IL-2(88Arg, 125Ala) fusion protein and the anti-tumor effects exerted by the fusion protein in HeLa-60 cells

et al. 2015

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Abstract. Gene therapy is a promising therapeutic option for the treatment of various cancers, and tumor-targeted plasmids encoding toxic protein genes are potential tools for gene therapy. In the present study, a recombinant plasmid containing the genes for the toxic protein melittin and interleukin-2 (IL-2) was constructed. Melittin and IL-2 are known to play key roles in immunoregulation and cancer therapy, but they each possess defects that limit the clinical application of these proteins. The present study aimed to construct a novel recombinant expression plasmid, pLEGFP-C1-M-IL-2(

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“…35 Using MHC class I-restricted TCR transgenic T cells from the OT-1 mouse, which are specific for the surrogate tumor Ag ovalbumin, our group also found that exogenous IL-2 promoted T-cell persistence after adoptive transfer, and donor CD8 þ T cells developed a memory phenotype based on CD44 and Ly6c expression. 36 In this study, we did not examine if the expression of the novel receptor N29g chR influences the fate of the transduced T cells in vivo. Such studies would help understand the mechanisms involved in transduced T cell-mediated tumor regression and the potential induction of systemic immunity and long-term antitumor responses.…”

Section: Discussionmentioning

confidence: 99%

Genetically engineered T cells expressing a HER2-specific chimeric receptor mediate antigen-specific tumor regression

Yang

Urban

et al. 2008

Cancer Gene Ther

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In this report, we developed a chimeric receptor (N29g chR) involving the single chain Fv (scFv) derived from N29 monoclonal antibody (mAb) specific for p185HER2 and characterized the therapeutic efficacy of primary T cells engineered to express N29g chR in two histologically distinct murine tumor models. Murine breast (MT901) and fibrosarcoma (MCA207) cancer cell lines were engineered to express human HER2 as targets. Administration of N29g chR-expressing T cells eliminated 3-day pulmonary micrometastases of MT901/HER2 and MCA207/HER2 but not parental tumor cells. A 5 to 8-fold increased dose of N29g T cells was required to mediate regression of advanced 8-day macrometastases. Exogenous administration of interleukin-2 (IL-2) after N29g T-cell transfer was dispensable for treatment of 3-day micrometastases, but was required for mediating regression of wellestablished 8-day macrometastases. Moreover, fractionated CD8 T cells expressing N29g chR suppressed HER2-positive tumor cell growth after adoptive transfer independent of CD4 þ cells. These data indicate that genetically modified T cells expressing a HER2-targeting chimeric receptor can mediate antigen-specific regression of preestablished metastatic cancers in a cell dose-dependent fashion. Systemic administration of IL-2 augments the therapeutic efficacy of these genetically engineered T cells in advanced diseases. These results are relevant to the implication of genetically redirected T cells in clinical cancer immunotherapy.

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Fate and function of anti-CD3/CD28-activated T cells following adoptive transfer: IL-2 promotes development of anti-tumor memory T cells in vivo

Cited by 9 publications

References 59 publications

Tc17 CD8+ T cells accumulate in murine atherosclerotic lesions, but do not contribute to early atherosclerosis development

Tc17 CD8+ T cells accumulate in murine atherosclerotic lesions, but do not contribute to early atherosclerosis development

Construction of the plasmid coding for the expression of the EGFP-M-IL-2(88Arg, 125Ala) fusion protein and the anti-tumor effects exerted by the fusion protein in HeLa-60 cells

Genetically engineered T cells expressing a HER2-specific chimeric receptor mediate antigen-specific tumor regression

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