Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Therapy of Established Tumors with Rationally Designed Multiple Agents Targeting Diverse Immune-Tumor Interactions: Engage, Expand, Enable

ABSTRACT: Therapy of Established Tumors with Rationally Designed Multiple Agents Targeting Diverse Immune-Tumor Interactions: Engage, Expand, Enable

PROVIDER: PRJNA683041 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Therapy of Established Tumors with Rationally Designed Multiple Agents Targeting Diverse Immune-Tumor Interactions: Engage, Expand, Enable

Project description:Immunotherapy of immunologically cold solid tumors may require multiple agents to (a) engage immune effector cells, (b) expand effector populations and activities, and (c) enable immune response in the tumor microenvironment (TME). To target these distinct phenomena, we strategically chose five clinical-stage immuno-oncology agents, namely, (a) a tumor antigen-targeting adenovirus-based vaccine (Ad-CEA) and an IL-15 superagonist (N-803) to activate tumor specific T cells, (b) OX40 and GITR agonists to expand and enhance the activated effector populations, and (c) an IDO inhibitor (IDOi) to enable effector cell activity in the TME. Flow cytometry, TCR sequencing, and RNAseq analyses showed that in the CEA-transgenic murine colon carcinoma (MC38-CEA) tumor model, Ad-CEA + N-803 combination therapy resulted in immune-mediated anti-tumor effects and promoted the expression of costimulatory molecules on immune subsets, OX40 and GITR, and the inhibitory molecule IDO. Treatment with Ad-CEA + N-803 + OX40 + GITR + IDOi, termed the pentatherapy regimen, resulted in the greatest inhibition of tumor growth and protection from tumor rechallenge without toxicity. Monotherapy with any of the agents had little to no anti-tumor activity, while combining two, three, or four agents had minimal anti-tumor effects. Immune analyses demonstrated that the pentatherapy combination induced CD4+ and CD8+ T cell activity in the periphery and tumor and anti-tumor activity associated with decreased Treg immunosuppression in the TME. The pentatherapy combination also inhibited tumor growth and metastatic formation in 4T1 and LL2-CEA murine tumor models. Significance: This study provides the rationale for the combination of multi-modal immunotherapy agents to engage, enhance, and enable adaptive anti-tumor immunity.

2021-02-10 | GSE162799 | GEO

Therapy of Established Tumors with Rationally Designed Multiple Agents Targeting Diverse Immune-Tumor Interactions: Engage, Expand, Enable.

Project description:Immunotherapy of immunologically cold solid tumors may require multiple agents to engage immune effector cells, expand effector populations and activities, and enable immune responses in the tumor microenvironment (TME). To target these distinct phenomena, we strategically chose five clinical-stage immuno-oncology agents, namely, (i) a tumor antigen-targeting adenovirus-based vaccine (Ad-CEA) and an IL15 superagonist (N-803) to activate tumor-specific T cells, (ii) OX40 and GITR agonists to expand and enhance the activated effector populations, and (iii) an IDO inhibitor (IDOi) to enable effector-cell activity in the TME. Flow cytometry, T-cell receptor (TCR) sequencing, and RNA-sequencing (RNA-seq) analyses showed that in the CEA-transgenic murine colon carcinoma (MC38-CEA) tumor model, Ad-CEA + N-803 combination therapy resulted in immune-mediated antitumor effects and promoted the expression of costimulatory molecules on immune subsets, OX40 and GITR, and the inhibitory molecule IDO. Treatment with Ad-CEA + N-803 + OX40 + GITR + IDOi, termed the pentatherapy regimen, resulted in the greatest inhibition of tumor growth and protection from tumor rechallenge without toxicity. Monotherapy with any of the agents had little to no antitumor activity, whereas combining two, three, or four agents had minimal antitumor effects. Immune analyses demonstrated that the pentatherapy combination induced CD4+ and CD8+ T-cell activity in the periphery and tumor, and antitumor activity associated with decreased regulatory T-cell (Treg) immunosuppression in the TME. The pentatherapy combination also inhibited tumor growth and metastatic formation in 4T1 and LL2-CEA murine tumor models. This study provides the rationale for the combination of multimodal immunotherapy agents to engage, enhance, and enable adaptive antitumor immunity.

| S-EPMC7864895 | biostudies-literature

A rationally designed JAZ subtype-selective agonist of jasmonate perception

Project description:A rationally designed JAZ subtype-selective agonist of jasmonate perception

| PRJNA434702 | ENA

Rationally designed, self-assembly, multifunctional hydrogel depot repairs severe spinal cord injury

Project description:Rationally designed, self-assembly, multifunctional hydrogel depot repairs severe spinal cord injury

| PRJNA695250 | ENA

Multiplexed characterization of rationally designed promoter architectures deconstructs combinatorial logic for IPTG-inducible systems

Project description:Multiplexed characterization of rationally designed promoter architectures deconstructs combinatorial logic for IPTG-inducible systems

| PRJNA607771 | ENA

Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis

Project description:GUT103 and GUT108, live biotherapeutic products rationally designed to complement missing or underrepresented functions in the dysbiotic microbiome of IBD patients; they address upstream targets, rather than targeting a single cytokine to block downstream inflammation responses. Systematic colonization experiments in colitis mouse models were performed to test their therapeutic effects. Targeted fecal metabolomics data uploaded here of bile acids, short-chain fatty acids, and tryptophan metabolites provides a unique metabolome perspective for evaluation of the therapeutic potential of GUT103 and GUT108.

2021-04-22 | ST001748 | MetabolomicsWorkbench

A rationally designed JAZ subtype-selective agonist of jasmonate perception

Project description:Gene expression profiles of WT, jaz9 and jaz10 mutant treated with mock or with 3, 6, or 8 was performed using the custom microarray Agilent-034592 The experiments were designed to explore the effect of antagonist of jasmonate perception in WT and two mutants

2018-08-05 | GSE110858 | GEO

Rationally designed immunogens enable immune focusing following SARS-CoV-2 spike imprinting.

Project description:Eliciting antibodies to surface-exposed viral glycoproteins can generate protective responses that control and prevent future infections. Targeting conserved sites may reduce the likelihood of viral escape and limit the spread of related viruses with pandemic potential. Here we leverage rational immunogen design to focus humoral responses on conserved epitopes. Using glycan engineering and epitope scaffolding in boosting immunogens, we focus murine serum antibody responses to conserved receptor binding motif (RBM) and receptor binding domain (RBD) epitopes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike imprinting. Although all engineered immunogens elicit a robust SARS-CoV-2-neutralizing serum response, RBM-focusing immunogens exhibit increased potency against related sarbecoviruses, SARS-CoV, WIV1-CoV, RaTG13-CoV, and SHC014-CoV; structural characterization of representative antibodies defines a conserved epitope. RBM-focused sera confer protection against SARS-CoV-2 challenge. Thus, RBM focusing is a promising strategy to elicit breadth across emerging sarbecoviruses without compromising SARS-CoV-2 protection. These engineering strategies are adaptable to other viral glycoproteins for targeting conserved epitopes.

| S-EPMC8898741 | biostudies-literature

ENGAGE Transcriptomics Flagship

Project description:ENGAGE Transcriptomics Flagship

| PRJEB3108 | ENA

Engage Project

Project description:Engage project for collaboration in next generation sequencing.

| PRJEB23868 | ENA