Immunotherapeutic effects of intratumoral nanoplexed Poly I:C (B16OVA tumors)
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PROVIDER: PRJNA476956 | ENA |
REPOSITORIES: ENA
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Project description:Immunotherapeutic effects of intratumoral nanoplexed Poly I:C
| PRJNA476961 | ENA
Project description:Poly I:C is a powerful immune adjuvant as a result of its agonist activities on TLR-3, MDA5 and RIG-I. Intratumoral administration is conceivably safer than systemic delivery and allows concentrate proinflammatory adjuvanticity in the tumor microenvironment and tumor-draining lymphoid tissue. BO-112 is a nanoplexed formulation of Poly I:C complexed with polyethylenimine that causes tumor cell apoptosis showing immunogenic cell death features and that upon intratumoral release results in more prominent tumor infiltration by T lymphocytes. Intratumoral treatment of subcutaneous tumors derived from MC38, 4T1 and B16F10 with BO-112 leads to remarkable local disease control mediated by CD8+ T lymphocytes, as concluded from selective depletion experiments. Some degree of control of non-injected tumor lesions upon BO-112 intratumoral treatment was found in mice bearing bilateral B16OVA melanomas, that was enhanced when co-treated with systemic anti-CD137 and anti-PD-L1 immunomodulatory mAbs. More abundant CD8+ T lymphocytes were found in tumor-draining lymph nodes and in the tumor microenvironment following intratumoral treatment with BO-112. Enhanced numbers of tumor-specific CTLs recognizing melanosomal antigens and ovalbumin were readily detected among them. Genome-wide transcriptome analyses of injected tumor lesions were consistent with a marked upregulation of the type-I interferon pathway. Intratumorally delivered BO-112 is being tested in cancer patients (NCT02828098) and our results in mice suggest prominent anti-tumor local control through its proimmune effects. Intratumoral administration of BO-112, a nanoplexed form of PolyI:C, triggers an efficacious antitumor response in different tumor models as a consequence of proimmflamatory activity and its direct effects in tumor cells. BO-112 local administration induces direct tumor cell death by apoptosis, showing signs of immunogenic cell death, and a strong release of IFNα/β and other proinflammatory mediators. As a result, a tumor-specific CD8+ immune response is mounted or augmented to the point of controlling tumor progression both in the locally injected lesion and to some extent on distantly implanted tumor nodules
2019-05-15 | GSE116074 | GEO
Project description:Immunotherapeutic effects of intratumoral nanoplexed Poly I:C (B16-OVA cell line)
| PRJNA476958 | ENA
Project description:Poly I:C is a powerful immune adjuvant as a result of its agonist activities on TLR-3, MDA5 and RIG-I. Intratumoral administration is conceivably safer than systemic delivery and allows concentrate proinflammatory adjuvanticity in the tumor microenvironment and tumor-draining lymphoid tissue. BO-112 is a nanoplexed formulation of Poly I:C complexed with polyethylenimine that causes tumor cell apoptosis showing immunogenic cell death features and that upon intratumoral release results in more prominent tumor infiltration by T lymphocytes. Intratumoral treatment of subcutaneous tumors derived from MC38, 4T1 and B16F10 with BO-112 leads to remarkable local disease control mediated by CD8+ T lymphocytes, as concluded from selective depletion experiments. Some degree of control of non-injected tumor lesions upon BO-112 intratumoral treatment was found in mice bearing bilateral B16OVA melanomas, that was enhanced when co-treated with systemic anti-CD137 and anti-PD-L1 immunomodulatory mAbs. More abundant CD8+ T lymphocytes were found in tumor-draining lymph nodes and in the tumor microenvironment following intratumoral treatment with BO-112. Enhanced numbers of tumor-specific CTLs recognizing melanosomal antigens and ovalbumin were readily detected among them. Genome-wide transcriptome analyses of injected tumor lesions were consistent with a marked upregulation of the type-I interferon pathway. Intratumorally delivered BO-112 is being tested in cancer patients (NCT02828098) and our results in mice suggest prominent anti-tumor local control through its proimmune effects. To compare the in-vitro and in vivo transcriptional profile induced by BO-112, B16-OVA cell lines were incubated with BO-112 for 24h. BO-112 induces a specific transcriptional profile in B16-OVA cell cultures. Key immunoregulatory genes were found to be differentially expressed between BO-112 and Vehicle-incubated B16-OVA cells.
2019-05-15 | GSE116075 | GEO
Project description:WEHI-164 tumors treated with intratumoral injections of poly(I:C), daily for 6 days
2023-06-04 | GSE229021 | GEO
Project description:Poly I:C is a powerful immune adjuvant as a result of its agonist activities on TLR-3, MDA5 and RIG-I. BO-112 is a nanoplexed formulation of Poly I:C complexed with polyethylenimine that causes tumor cell apoptosis showing immunogenic cell death features and which upon intratumoral release results in more prominent tumor infiltration by T lymphocytes. Intratumoral treatment with BO-112 of subcutaneous tumors derived from MC38, 4 T1 and B16-F10 leads to remarkable local disease control dependent on type-1 interferon and gamma-interferon. Some degree of control of non-injected tumor lesions following BO-112 intratumoral treatment was found in mice bearing bilateral B16-OVA melanomas, an activity which was enhanced with co-treatment with systemic anti-CD137 and anti-PD-L1 mAbs. More abundant CD8+ T lymphocytes were found in B16-OVA tumor-draining lymph nodes and in the tumor microenvironment following intratumoral BO-112 treatment, with enhanced numbers of tumor antigen-specific cytotoxic T lymphocytes. Genome-wide transcriptome analyses of injected tumor lesions were consistent with a marked upregulation of the type-I interferon pathway. Inspired by these data, intratumorally delivered BO-112 is being tested in cancer patients (NCT02828098).
| S-EPMC6498680 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-05-15 | GSE116078 | GEO
Project description:This study explores the synergistic antitumor potential of Poly(I:C) and QS-21 in melanoma treatment. Through in vitro assays and animal models, we evaluated their combined impact on melanoma cell proliferation, apoptosis, and immune response. Our results indicate that Poly(I:C), an immunostimulant, activates the immune system to bolster antitumor activity. QS-21, an immunological adjuvant, enhances Poly(I:C)'s effects, together acting as an in situ vaccine to expose neoantigens and reignite the tumor-immune interaction. This research offers a promising immunotherapeutic approach for melanoma.
2025-01-31 | GSE287957 | GEO
Project description:In syngeneic solid tumor models, C5aR1 inhibition significantly enhanced the effectiveness of poly I:C, a toll-like receptor 3 (TLR3) agonist, combined with Programmed cell death protein 1 (PD-1)/Programmed cell death ligand-1 (PD-L1) blockade. In this experiment we aim to determine the effects of C5aR1 inhibition in the genes expression of Lewis Lung Cancer (LLC) tumors treated with poly I:C and PD-1 blockade combined treatment.
2024-11-20 | GSE239485 | GEO
Project description:We designed a novel intratumoral (IT) IL-12 mRNA therapy to promote local IL-12 tumor production whilst mitigating systemic effects. A single IT dose of mouse (m)IL-12 mRNA induced IFNγ and CD8+ T cell-dependent tumor regression in multiple syngeneic mouse models including MC38-R, and animals with a complete response demonstrated immunity to re-challenge. In order to further investigate the impact of mIL-12 mRNA on the MC38-R TME, we performed tumor transcriptomic evaluation 24h and 7 days after a single IT dose of 0.5 micrograms IL-12 or control mRNA. mRNA was isolated from snap-frozen syngeneic tumors using an RNeasy mini kit (Qiagen) and quantified on the Affymetrix mouse 430 2.0 microarray.
2020-09-01 | E-MTAB-9316 | biostudies-arrayexpress