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TCR repertoire and transcriptomic analyses of advanced solid tumors in first-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody

ABSTRACT: TCR repertoire and transcriptomic analyses of advanced solid tumors in first-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody

PROVIDER: PRJNA491656 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7868530.fastq.gz	Fastqsanger.gz
	SRR7868540.fastq.gz	Fastqsanger.gz
	SRR7868550.fastq.gz	Fastqsanger.gz
	SRR7868560.fastq.gz	Fastqsanger.gz
	SRR7868570.fastq.gz	Fastqsanger.gz

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Similar Datasets

T-cell receptor repertoire analysis of advanced solid tumors in first-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody [TCR-seq]

Project description:Immune checkpoint inhibitors such as anti-cytotoxic T-lymphocyte–associated antigen-4 and anti-programmed cell death-1 monoclonal antibodies (mAbs) agents or these combinations has improved outcomes of various cancers.However, still not a few patients fail to achieve clinical benefit, this highlights the importance of additional treatment to overcome its resistance. Previously, we showed that administration of the anti-CD4 mAb alone had strong anti-tumor effects that were superior to those elicited by CD25+ Treg depletion or other immune checkpoint mAbs in B16F10, Colon 26, or Lewis lung carcinoma subcutaneous tumor models. IT1208 (IDAC Theranostics, Tokyo, Japan) is a humanized anti-CD4 immunoglobulin G1 (IgG1) monoclonal antibody with a defucosylated Fc region, which markedly enhances antibody dependent cellular cytotoxicity. In a first-in-human, phase I, open-label, dose-escalation study, we performed T cell repertoire analysis of T cell subsets in the tumors and peripheral blood mononuclear cells (PBMCs) to clarify T cell responses against IT1208 monotherapy in patients with advanced solid tumors.

2019-08-06 | GSE120101 | GEO

T-cell receptor repertoire analysis of advanced solid tumors in first-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody [TCR-seq]

Project description:T-cell receptor repertoire analysis of advanced solid tumors in first-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody [TCR-seq]

| PRJNA491658 | ENA

Transcriptomic analysis of advanced solid tumors in first-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody [3'SAGE-seq]

Project description:Immune checkpoint inhibitors such as anti-cytotoxic T-lymphocyte–associated antigen-4 and anti-programmed cell death-1 monoclonal antibodies (mAbs) agents or these combinations has improved outcomes of various cancers.However, still not a few patients fail to achieve clinical benefit, this highlights the importance of additional treatment to overcome its resistance. Previously, we showed that administration of the anti-CD4 mAb alone had strong anti-tumor effects that were superior to those elicited by CD25+ Treg depletion or other immune checkpoint mAbs in B16F10, Colon 26, or Lewis lung carcinoma subcutaneous tumor models. IT1208 (IDAC Theranostics, Tokyo, Japan) is a humanized anti-CD4 immunoglobulin G1 (IgG1) monoclonal antibody with a defucosylated Fc region, which markedly enhances antibody dependent cellular cytotoxicity. In a first-in-human, phase I, open-label, dose-escalation study, we performed transcriptomic analysis of tumors to clarify molecular responses against IT1208 monotherapy in patients with advanced solid tumors.

2019-08-06 | GSE120028 | GEO

TCR repertoire and transcriptomic analyses of advanced solid tumors in first-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody

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

2019-08-06 | GSE120102 | GEO

Transcriptomic analysis of advanced solid tumors in first-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody [3'SAGE-seq]

Project description:Transcriptomic analysis of advanced solid tumors in first-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody [3'SAGE-seq]

| PRJNA491654 | ENA

First-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody, in patients with advanced solid tumors.

Project description:BackgroundTransient CD4+ T cell depletion led to the proliferation of tumor-specific CD8+ T cells in the draining lymph node and increased infiltration of PD-1+CD8+ T cells into the tumor, which resulted in strong anti-tumor effects in tumor-bearing mice. This is a first-in-human study of IT1208, a defucosylated humanized anti-CD4 monoclonal antibody, engineered to exert potent antibody-dependent cellular cytotoxicity.MethodsPatients with advanced solid tumors were treated with intravenous IT1208 at doses of 0.1 or 1.0 mg/kg. The first patient in each cohort received a single administration, and the other patients received two administrations of IT1208 on days 1 and 8.ResultsEleven patients were enrolled in the 0.1 mg/kg (n = 4) and 1.0 mg/kg cohorts (n = 7). Grade 1 or 2 infusion-related reactions was observed in all patients. Decreased CD4+ T cells in peripheral blood due to IT1208 were observed in all patients and especially in those receiving two administrations of 1.0 mg/kg. CD8+ T cells increased on day 29 compared with baseline in most patients, resulting in remarkably decreased CD4/8 ratios. One microsatellite-stable colon cancer patient achieved durable partial response showing increased infiltration of both CD4+ and CD8+ T cells into tumors after IT1208 administration. Moreover, transcriptomic profiling of the liver metastasis of the patient revealed upregulation of the expression of interferon-stimulated genes, T cell activation-related genes, and antigen presentation-related genes after IT1208 administration. Two additional patients with gastric or esophageal cancer achieved stable disease lasting at least 3 months.ConclusionsIT1208 monotherapy successfully depleted CD4+ T cells with a manageable safety profile and encouraging preliminary efficacy signals, which warrants further investigations, especially in combination with immune checkpoint inhibitors.

| S-EPMC6657210 | biostudies-literature

Maytansinoid DM4-Conjugated Humanized Monoclonal Antibody huC242 in Treating Patients With Solid Tumors

Project description:RATIONALE: Monoclonal antibodies, such as maytansinoid DM4-conjugated humanized monoclonal antibody huC242, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. PURPOSE: This phase I trial is studying the side effects and best dose of maytansinoid DM4-conjugated humanized monoclonal antibody huC242 in treating patients with solid tumors that cannot be removed by surgery or have spread to other parts of the body.

| 2030868 | ecrin-mdr-crc

Advanced Genetic and Molecular Analysis of Solid Tumors

Project description:Advanced Genetic and Molecular Analysis of Solid Tumors

| PRJNA615692 | ENA

Advanced Genetic and Molecular Analysis of Solid Tumors

Project description:Advanced Genetic and Molecular Analysis of Solid Tumors

| PRJNA615693 | ENA

First-in-class microbial ecosystem therapeutics 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumours (MET4-IO Trial)

Project description:The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICI) in humans, and causally implicated in ICI responsiveness in animal models. Therapeutic augmentation of the microbiome in ICI recipients is being investigated in multiple ongoing human clinical trials. We conducted an early phase clinical trial of a cultivated, orally-delivered 30-species microbial consortium (microbial ecosystem therapeutic-4, MET4) designed for co-administration with ICIs and assessed safety, tolerability and ecological responses in patients with advanced solid tumors.

2022-03-26 | GSE199245 | GEO

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