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Robust antitumor activity of a de novo interleukin-21 mimic

ABSTRACT: Robust antitumor activity of a de novo interleukin-21 mimic

PROVIDER: PRJNA1078872 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28037635.fastq.gz	Fastqsanger.gz
	SRR28037636.fastq.gz	Fastqsanger.gz
	SRR28037637.fastq.gz	Fastqsanger.gz
	SRR28037638.fastq.gz	Fastqsanger.gz
	SRR28037639.fastq.gz	Fastqsanger.gz

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Robust antitumor activity of a de novo interleukin-21 mimic

Project description:A long-standing goal of cancer immunotherapy is to activate cytotoxic antitumor T cells across a broad range of affinities and dampen suppressive regulatory T (Treg) cell responses, but current approaches achieve these goals with limited success. Here, we report a de novo IL-21 mimic, 21h10, designed to have augmented stability and high signaling potency in both humans and mice. In multiple animal models, 21h10 showed robust antitumor activity, exceeding that of native IL-21 for murine melanoma, inducing a rapid regression of murine adenocarcinoma, and exhibiting potent activity in an orthotopic pancreatic cancer model that is refractory to conventional immunotherapies. In the tumor microenvironment, 21h10 induced highly cytotoxic antitumor T cells from clonotypes with a range of affinities for endogenous tumor antigens, driving high expression of interferon- (IFN- ) and granzyme B compared to native IL-21, while in the CD4+ T cell compartment, the frequency of IFN- + Th1 cells was increased while Foxp3+ Treg cells were reduced. Thus, 21h10 is a highly active IL-21 mimic with human-mouse cross-reactivity that potentiates low-affinity antitumor responses and has considerable translational potential.

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Interleukin-10/CSF1R fusion protein rejuvenates the exhausted T cells for executing antitumor activity II

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Interleukin-10/CSF1R fusion protein rejuvenates the exhausted T cells for executing antitumor activity V

Project description:Interleukin-10/CSF1R fusion protein rejuvenates the exhausted T cells for executing antitumor activity V

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Project description:Interleukin-10/CSF1R fusion protein rejuvenates the exhausted T cells for executing antitumor activity IV

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Interleukin-10/CSF1R fusion protein rejuvenates the exhausted T cells for executing antitumor activity III

Project description:Interleukin-10/CSF1R fusion protein rejuvenates the exhausted T cells for executing antitumor activity III

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