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Collagen-anchored interleukin-2 and interleukin-12 safely reprogram the tumor microenvironment in canine soft tissue sarcomas

ABSTRACT: Collagen-anchored interleukin-2 and interleukin-12 safely reprogram the tumor microenvironment in canine soft tissue sarcomas

PROVIDER: PRJNA906127 | ENA |

REPOSITORIES: ENA

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Collagen-anchored interleukin-2 and interleukin-12 safely reprogram the tumor microenvironment in soft tissue sarcomas

Project description:Collagen-anchored interleukin-2 and interleukin-12 safely reprogram the tumor microenvironment in soft tissue sarcomas

| PRJNA906123 | ENA

Collagen-anchored interleukin-2 and interleukin-12 safely reprogram the tumor microenvironment in canine soft tissue sarcomas

Project description:Canine soft tissue sarcomas were analyzed for gene expression changes following intratumoral treatment with collagen-anchored IL-2 and IL-12 therapy. Tumors were surgically resected at different intervals following treatment to assess persistence of any therapy-driven gene expression changes.

2023-03-01 | GSE218912 | GEO

Collagen-anchored interleukin-2 and interleukin-12 safely reprogram the tumor microenvironment in mouse melanomas

Project description:Mouse B16F10 melanoma tumors were analyzed for gene expression changes following intratumoral treatment with collagen-anchored IL-2 and IL-12 therapy for comparative analysis to expression changes observed in canine soft tissue sarcomas. Tumors were collected at different intervals following treatment to assess persistence of any therapy-driven gene expression changes.

2023-03-01 | GSE218913 | GEO

Collagen-anchored interleukin-2 and interleukin-12 safely reprogram the tumor microenvironment in mouse melanomas

Project description:Collagen-anchored interleukin-2 and interleukin-12 safely reprogram the tumor microenvironment in mouse melanomas

| PRJNA906126 | ENA

Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas.

Project description:PurposeCytokine therapies such as IL2 and IL12 suffer from impractically small therapeutic windows driven by their on-target, off-tumor activity, limiting their clinical potential despite potent antitumor effects. We previously engineered cytokines that bind and anchor to tumor collagen following intratumoral injection, and sought to test their safety and biomarker activity in spontaneous canine soft-tissue sarcomas (STS).Experimental designCollagen-binding cytokines were canine-ized to minimize immunogenicity and were used in a rapid dose-escalation study in healthy beagles to identify a maximum tolerated dose. Ten client-owned pet dogs with STS were then enrolled into trial, receiving cytokines at different intervals prior to surgical tumor excision. Tumor tissue was analyzed through IHC and NanoString RNA profiling for dynamic changes within treated tumors. Archived, untreated STS samples were analyzed in parallel as controls.ResultsIntratumorally administered collagen-binding IL2 and IL12 were well tolerated by STS-bearing dogs, with only Grade 1/2 adverse events observed (mild fever, thrombocytopenia, neutropenia). IHC revealed enhanced T-cell infiltrates, corroborated by an enhancement in gene expression associated with cytotoxic immune function. We found concordant increases in expression of counter-regulatory genes that we hypothesize would contribute to a transient antitumor effect, and confirmed in mouse models that combination therapy to inhibit this counter-regulation can improve responses to cytokine therapy.ConclusionsThese results support the safety and activity of intratumorally delivered, collagen-anchoring cytokines for inflammatory polarization of the canine STS tumor microenvironment. We are further evaluating the efficacy of this approach in additional canine cancers, including oral malignant melanoma.

| S-EPMC10239368 | biostudies-literature

Collagen-anchored interleukin-2 and interleukin-12 safely reprogram the tumor microenvironment in soft tissue sarcomas

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-03-01 | GSE218914 | GEO

20 human soft-tissue sarcomas (TMT)

Project description:SCX fractiond, TMT labeled pleomorphic soft-tissue sarcomas. 32 raw files (8x4) plus 8 pools (also TMT labeled) corresponding to each SCX fraction are submitted. The latter were used to propagate identifications across the runs.

2020-01-27 | PXD000617 | Pride

The Proteomic Landscape of Soft Tissue Sarcomas

Project description:Soft tissue sarcomas (STS) are rare and diverse mesenchymal cancers with limited treatment options. Here we undertake comprehensive proteomic profiling of formalin-fixed paraffin embedded tumour specimens from 321 STS patients representing 11 histological subtypes.

2023-05-09 | PXD036226 | Pride

Spatial transcriptomics analysis of soft tissue sarcomas.

Project description:The tumor microenvironment plays a crucial role in soft tissue sarcoma development and response to therapy. We used spatial transcriptomics to analyze the spatial distribution of malignant, immune, and other stromal cells present within soft tissue sarcomas.

2023-12-12 | GSE212526 | GEO

Nitrocamptothecin in Treating Patients With Soft Tissue Sarcomas

Project description:RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of nitrocamptothecin in treating patients who have locally advanced or metastatic soft tissue sarcomas.

| 2004949 | ecrin-mdr-crc

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