Transcriptomes of 4T1-HA tumors treated with anti-PD-1 and IL-12 micelle
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE196030 | GEO | 2023/04/13
REPOSITORIES: GEO
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Project description:Transcriptomes of 4T1-HA tumors treated with anti-PD-1 and IL-12 micelle
| PRJNA803056 | ENA
Project description:Analysis of the effect of anti-IL-15 monoclonal antibody treatment on T cell and NK cell homeostasis in rhesus macaques. The hypothesis tested in the present study was that repeated administrations of a rhesusized anti-IL-15 monoclonal antibody would block IL-15 activity in vivo and result in changes to T and/or NK cell population dynamics that would reflect physiologic IL-15 function. The results provide important information on the specific role IL-15 plays in effector memory T cell and NK cell homeostasis, noting that effector memory T cells but not NK cells can be maintained in the absence of IL-15 signaling by the activity of other cytokines. Sort-purified CD8+ and CD4+ TCM from PBMC, before and after treatment with IgG1 Ab and anti-IL15 Ab
2016-09-07 | E-GEOD-76785 | biostudies-arrayexpress
Project description:Analysis of the effect of anti-IL-15 monoclonal antibody treatment on T cell and NK cell homeostasis in rhesus macaques. The hypothesis tested in the present study was that repeated administrations of a rhesusized anti-IL-15 monoclonal antibody would block IL-15 activity in vivo and result in changes to T and/or NK cell population dynamics that would reflect physiologic IL-15 function. The results provide important information on the specific role IL-15 plays in effector memory T cell and NK cell homeostasis, noting that effector memory T cells but not NK cells can be maintained in the absence of IL-15 signaling by the activity of other cytokines. Sort-purified CD8+ TEM from PBMC, before and after treatment with IgG1 Ab and anti-IL15 Ab
2016-09-07 | E-GEOD-76796 | biostudies-arrayexpress
Project description:IL-27, a member of the IL-12- family of cytokines, has shown anti-tumor activity in several pre-clinical models due to anti-proliferative, anti-angiogenic and immune-enhancing effects. On the other hand, IL-27 demonstrated immune-regulatory activities and inhibition of auto-immunity in mouse models. Also, we reported that IL-27, similar to IFN-, induces the expression of IL-18BP, IDO and PD-L1 immune-regulatory molecules in human cancer cells. Here, a proteomic analysis reveals that IL-27 and IFN- display a broad overlap of functions on human ovarian cancer cells. Indeed, among 990 proteins modulated by either cytokine treatment in SKOV3 cells, 814 showed a concordant modulation by both cytokines, while a smaller number (176) were differentially modulated. The most up-regulated proteins were common to both IFN-γ and IL-27. In addition, functional analysis of IL-27- regulated protein networks highlighted pathways of interferon signaling and regulation, antigen presentation, protection from natural killer cell-mediated cytotoxicity, regulation of protein polyubiquitination and proteasome, aminoacid catabolism and regulation of viral protein levels.
2017-05-19 | PXD004419 | Pride
Project description:Analysis of the effect of anti-IL-15 monoclonal antibody treatment on T cell and NK cell homeostasis in rhesus macaques. The hypothesis tested in the present study was that repeated administrations of a rhesusized anti-IL-15 monoclonal antibody would block IL-15 activity in vivo and result in changes to T and/or NK cell population dynamics that would reflect physiologic IL-15 function. The results provide important information on the specific role IL-15 plays in effector memory T cell and NK cell homeostasis, noting that effector memory T cells but not NK cells can be maintained in the absence of IL-15 signaling by the activity of other cytokines.
2016-09-07 | GSE76796 | GEO
Project description:Analysis of the effect of anti-IL-15 monoclonal antibody treatment on T cell and NK cell homeostasis in rhesus macaques. The hypothesis tested in the present study was that repeated administrations of a rhesusized anti-IL-15 monoclonal antibody would block IL-15 activity in vivo and result in changes to T and/or NK cell population dynamics that would reflect physiologic IL-15 function. The results provide important information on the specific role IL-15 plays in effector memory T cell and NK cell homeostasis, noting that effector memory T cells but not NK cells can be maintained in the absence of IL-15 signaling by the activity of other cytokines.
2016-09-07 | GSE76785 | GEO
Project description:Systemic administration of interleukin (IL)-12 has been shown to induce potent anti-tumor immune responses in preclinical cancer models. Previous clinical trials using bolus IL-12 injection through maximal tolerable dosing (MTD) strategies indicated limited efficacy alongside unwanted side-effects. Our group developed IL-12-loaded PLGA nanospheres (IL12ns) that release their contents systemically in a slow, controlled manner. An immune diagnostic platform (IDP), capable of monitoring therapeutic response through peripheral blood sampling, was designed alongside this immunostimulatory therapy. The systemic immune responses from MTD and IL12ns dosing strategies were analyzed using this IDP in healthy mice. Importantly, the MTD was associated with aberrant peripheral immune stimulation, evidenced by increased IL-12, interferon gamma (IFNG), and IL-10 signaling. The immune-protective effects of IL12ns were supported by increases in pro-inflammatory plasma cytokines/chemokines without the maladaptive transcriptomic signatures in circulating peripheral immune cells. These data ultimately support the necessity of a vector system for safe immunostimulatory IL-12 therapy.
2024-01-16 | GSE241939 | GEO
Project description:By their selective infection or replication into tumors, oncolytic viruses trigger profound modifications of tumor immune microenvironment with a massive infiltration and activation of T cells. This tumor warming up can be further amplified by the local delivery of powerful immunomodulatory molecules encoded into virus’ genome. Those properties are particularly of interest for tumor poorly infiltrated or infiltrated with anergic T cells to reverse patient’s unresponsiveness to immune checkpoint inhibitors (ICI). TG6050 is a new oncolytic vaccinia virus encoding single-chain human Interleukin-12 (hIL-12) and full length anti-cytotoxic T-lymphocyte-associated antigen-4 (@CTLA-4) monoclonal antibody. Replication, oncolysis, selectivity, transgenes expression and functionality of TG6050 were characterized in vitro. Virus and IL-12 pharmacokinetics, antitumoral activities (alone or combined with ICI), and mechanism of action (MOA) were investigated in “hot” (highly infiltrated) and “cold” (poorly infiltrated) syngeneic murine tumor models. MOA was deciphered by monitoring both systemic and tumor immune responses, and tumor transcriptome analyses. Finally, TG6050 safety after repeated intravenous administrations was evaluated in cynomolgus monkeys and special attention was paid to the level of circulating IL-12 potentially associated with toxic effects. In vitro or in vivo replication of TG6050 in tumor cells allows local expression of functional IL-12 and @CTLA-4. The expression of transgenes, together with the virus replication, translated into an antitumoral activity in both “cold and “hot” tumor murine models that was further amplified by combination with ICI. Analysis of tumor microenvironment (TME) after TG6050 treatment showed an increase of interferon gamma, CD8+ T cells, M1/M2 macrophages ratio and a drastic decrease of regulatory T cells. Those local modifications were observed together with an enhanced systemic and specific antitumor adaptive immune response. In toxicology studies, the virus did not produce any observable adverse effects in cynomolgus monkeys. Conclusions: TG6050 allows the delivery of functional IL-12 and @CTLA-4 into tumor resulting in an excellent antitumor activity along with a shift towards an inflamed TME, and a boost of the systemic antitumor T-cells. Toxicological studies in macaques demonstrated the safety of TG6050. Together these results paved the way for clinical evaluation of TG6050 in metastatic non-small cell lung cancer (NCT05788926).
2024-07-30 | GSE259380 | GEO
Project description:By their selective infection or replication into tumors, oncolytic viruses trigger profound modifications of tumor immune microenvironment with a massive infiltration and activation of T cells. This tumor warming up can be further amplified by the local delivery of powerful immunomodulatory molecules encoded into virus’ genome. Those properties are particularly of interest for tumor poorly infiltrated or infiltrated with anergic T cells to reverse patient’s unresponsiveness to immune checkpoint inhibitors (ICI). TG6050 is a new oncolytic vaccinia virus encoding single-chain human Interleukin-12 (hIL-12) and full length anti-cytotoxic T-lymphocyte-associated antigen-4 (@CTLA-4) monoclonal antibody. Replication, oncolysis, selectivity, transgenes expression and functionality of TG6050 were characterized in vitro. Virus and IL-12 pharmacokinetics, antitumoral activities (alone or combined with ICI), and mechanism of action (MOA) were investigated in “hot” (highly infiltrated) and “cold” (poorly infiltrated) syngeneic murine tumor models. MOA was deciphered by monitoring both systemic and tumor immune responses, and tumor transcriptome analyses. Finally, TG6050 safety after repeated intravenous administrations was evaluated in cynomolgus monkeys and special attention was paid to the level of circulating IL-12 potentially associated with toxic effects. In vitro or in vivo replication of TG6050 in tumor cells allows local expression of functional IL-12 and @CTLA-4. The expression of transgenes, together with the virus replication, translated into an antitumoral activity in both “cold and “hot” tumor murine models that was further amplified by combination with ICI. Analysis of tumor microenvironment (TME) after TG6050 treatment showed an increase of interferon gamma, CD8+ T cells, M1/M2 macrophages ratio and a drastic decrease of regulatory T cells. Those local modifications were observed together with an enhanced systemic and specific antitumor adaptive immune response. In toxicology studies, the virus did not produce any observable adverse effects in cynomolgus monkeys. Conclusions: TG6050 allows the delivery of functional IL-12 and @CTLA-4 into tumor resulting in an excellent antitumor activity along with a shift towards an inflamed TME, and a boost of the systemic antitumor T-cells. Toxicological studies in macaques demonstrated the safety of TG6050. Together these results paved the way for clinical evaluation of TG6050 in metastatic non-small cell lung cancer (NCT05788926).
2024-07-30 | GSE259379 | GEO
Project description:NK cells are a promising cellular therapy for cancer, with challenges in the field including persistence, functional activity, and tumor recognition. Briefly priming blood NK cells with rhIL-12, rhIL-15, and rhIL-18 (12/15/18) results in memory-like NK cell differentiation and enhanced responses against cancer. We developed a novel platform centered upon an inert tissue factor scaffold for production of heteromeric fusion protein complexes (HFPC). The first use of this platform combined IL-12, IL-15 and IL-18 receptor engagement (HCW9201) and the second adds CD16 engagement (HCW9207). HCW9201 and HCW9207 stimulated activation and proliferation signals in NK cells, but HCW9207 had decreased IL-18 receptor signaling. RNAseq and multidimensional mass cytometry revealed strong parallels between HCW9201 and 12/15/18. Moreover, HCW9201 stimulation improved NK cell metabolic fitness, and resulted in the DNA methylation remodeling characteristic of memory-like differentiation. HCW9201- and 12/15/18-primed similar increases in short-term and memory-like NK cell cytotoxicity and IFN-g production against leukemia targets, as well as equivalent control of leukemia in NSG mice. Thus, HFPCs represent a protein engineering approach that solves many problems associated with multi-signal receptor engagement on immune cells, and HCW9201-primed NK cells will be advanced as an ideal approach for clinical GMP-grade memory-like NK cell production for cancer therapy.erm and memory-like NK cell cytotoxicity and IFN-g production against leukemia targets, as well as equivalent control of leukemia in NSG mice. Thus, HFPCs represent a protein engineering approach that solves many problems associated with multi-signal receptor engagement on immune cells, and HCW9201-primed NK cells will be advanced as an ideal approach for clinical GMP-grade memory-like NK cell production for cancer therapy.
2021-04-15 | GSE172100 | GEO