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

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

PROVIDER: PRJNA906126 | 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:Collagen-anchored interleukin-2 and interleukin-12 safely reprogram the tumor microenvironment in canine soft tissue sarcomas

| PRJNA906127 | ENA

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 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 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

Characterization of resistance to tumor-localized interleukin-2 and interleukin-12 therapy in pet dogs with advanced malignant melanoma

Project description:Pet dogs with oral melanoma were treated in a dose-escalation trial with collagen-anchored interleukin-2 and interleukin-12 following a single 9Gy dose of radiation therapy. Dogs that progressed during, or after, treatment and were ultimately euthanized had tissue collected from primary and metastatic tumors to analyze gene expression and assess mechanisms of resistance to this therapy.

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Whole exome sequencing of human primary uveal melanomas

Project description:Primary uveal melanomas show multiple genetic alterations. To determine mutational status of six human primary uveal melanomas, we performed whole exome sequencing (WES) and called Single Nucleotide Polimorphism (SNPs) to identify somatic mutations in these human primary uveal melanomas.

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Molecular characterization of mucosal melanomas

Project description:Molecular characterization of mucosal melanomas

| PRJNA470997 | ENA

Molecular characterization of mucosal melanomas

Project description:Molecular characterization of mucosal melanomas

| PRJNA470998 | ENA