Dataset Information

Targeted protein editing with an antibody-based system

ABSTRACT: The chemical modification of proteins is one of the major mechanisms used to regulate the properties and functions of these macromolecules in the cell. It is therefore of great interest to develop tools to exploit this type of modifications for applications in molecular biology, medicine and biotechnology. Here we present a method of using antibodies to perform post-translational covalent modifications of endogenous proteins in complex environments by exploiting proximity-driven chemistry. The method is based on the ability of antibodies to hold a weakly reactive group close to its intended site of reaction by binding the target protein on a nearby epitope. We characterise this approach by modifying the green fluorescent protein in increasingly complex environments, and illustrate its applicability by targeting the disease-associated protein beta-2 microglobulin. This dataset contains proteomics data for the identification of the modification site(s) on PEABS targets.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Aequorea Victoria

SUBMITTER: Oded Rimon

LAB HEAD: Michele Vendruscolo

PROVIDER: PXD049693 | Pride | 2025-09-08

REPOSITORIES: Pride

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Targeted Protein Modification with an Antibody-Based System.

Rimon Oded O Konc Juraj J Černauskienė Inga I Ali Montader M Roy Chowdhury Vaidehi V Sormanni Pietro P Bernardes Gonçalo J L GJL Vendruscolo Michele M

ACS central science 20250707 8

The chemical modification of proteins is one of the major mechanisms used to regulate the properties and functions of these macromolecules in the cell. It is therefore of great interest to develop tools to exploit this type of modification for applications in molecular biology, medicine, and biotechnology. Here we present a method of using antibodies to perform post-translational covalent modifications of endogenous proteins in complex environments by exploiting proximity-driven chemistry. The m ...[more]

PMID: 40893970

Similar Datasets

Project description:Background Clinical success of T cell receptor (TCR) gene therapy has previously been demonstrated for NY-ESO-1 TCR gene therapy. To increase numbers of cancer patients that can be treated with TCR gene therapy we aimed to identify a novel set of high-affinity cancer specific TCRs targeting different cancer testis (CT) antigens in prevalent HLA class I alleles. Methods In this study, we selected based on publicly available gene expression databases the most promising CT genes to target. From these selected genes we identified by HLA peptidomics the naturally processed and presented HLA class I peptides. With these peptide-HLA tetramers were generated, and by single cell sorting CT specific CD8+ T cells were selected, and expanded from the allo-HLA repertoire of healthy donors. By several functional assays high avidity CT-specific T cell clones with safe recognition pattern were selected. To evaluate the potential for clinical application in TCR gene therapy, TCRs were sequenced and transferred into peripheral blood derived CD8+ T cells. Results In total we identified, 7 novel CT-specific TCRs that effectively target MAGE-A1, MAGE-A3, MAGE-A6 and MAGE-A9 in the context of human leukocyte antigen(HLA) -A1, -A2, -A3, -B7, -B35 and -C7. TCR gene transfer into CD8⁺ T cells resulted in efficient cytokine production and cytotoxicity of variety of different tumor types without detectable cross-reactivity. In addition, major in vivo antitumor effects of MAGE-A1 specific TCR engineered CD8⁺ T cells was observed in an orthotopic xenograft model for established multiple myeloma, in which bone marrow located tumor cells were completely eradicated after T cell injection. Conclusion The identification of 7 novel CT-specific TCRs, reactive against CT antigens presented in a variety of different HLA class I alleles, allows selection of therapeutic TCRs for an increased number of cancer patients, and will improve development of personalized TCR gene therapy.

			Action	DRS
	P1423_GFP_bio.dat	Other
	P1423_GFP_bio.mht	Other
	P1423_GFP_bio.raw	Raw
	P1423_GFP_rho.dat	Other
	P1423_GFP_rho.mht	Other