AR114735A1 - METHOD FOR ULTRA-RAPID AFFINITY SCREENING OF MHC-PEPTIDE COMPLEXES IN SEARCH OF TCR LIGANDS - Google Patents

METHOD FOR ULTRA-RAPID AFFINITY SCREENING OF MHC-PEPTIDE COMPLEXES IN SEARCH OF TCR LIGANDS

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Publication number
AR114735A1
AR114735A1 ARP190102633A ARP190102633A AR114735A1 AR 114735 A1 AR114735 A1 AR 114735A1 AR P190102633 A ARP190102633 A AR P190102633A AR P190102633 A ARP190102633 A AR P190102633A AR 114735 A1 AR114735 A1 AR 114735A1
Authority
AR
Argentina
Prior art keywords
mhc
domain
molecule
stabilized
mhc molecule
Prior art date
Application number
ARP190102633A
Other languages
Spanish (es)
Inventor
Claudia Wagner
Sebastian Bunk
Dominik Maurer
Andreas Moritz
Original Assignee
Immatics Biotechnologies Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Immatics Biotechnologies Gmbh filed Critical Immatics Biotechnologies Gmbh
Publication of AR114735A1 publication Critical patent/AR114735A1/en

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  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La presente concierne a un método para el cribado ultrarrápido para identificar un complejo que se une a un TCR constituido por una molécula del MHC y un ligando peptídico, el cual comprende una molécula de MHC-péptido estabilizada y los usos respectivos de dicho método. La presente concierne, además, a polipéptidos que comprenden o consisten en moléculas MHC estabilizadas o en fragmentos de unión a péptidos de las mismas, a composiciones farmacéuticas que comprenden dichos polipéptidos, vacunas que comprenden dicha composición farmacéutica y usos de dicha vacuna para la fabricación de un medicamento y/o para la prevención del cáncer. La presente concierne, además, a ácidos nucleicos que codifican dichos polipéptidos y a vectores que comprenden dichos ácidos nucleicos. Reivindicación 1: Método para el cribado de un complejo que se une a un TCR formado por una molécula del MHC y un ligando peptídico (pMHC), que comprende las etapas siguientes: a) proporcionar una molécula del MHC convenientemente estabilizada, en que dicha molécula del MHC comprende al menos un puente covalente artificialmente introducido: (I) entre un aminoácido del dominio a-1 y un aminoácido del dominio a-2 de dicha molécula del MHC estabilizada en el caso del MHC I; y/o (II) entre dos aminoácidos del dominio a-1 de dicha molécula del MHC estabilizada en el caso del MHC I; o (III) entre dos aminoácidos del dominio a-1 o del dominio b-1 de dicha molécula del MHC estabilizada en el caso del MHC II; y/o (IV) entre un aminoácido del dominio a-1 y un aminoácido del dominio b-1 de dicha molécula del MHC estabilizada en el caso del MHC II; b) la puesta en contacto de dicha molécula del MHC convenientemente estabilizada con una multitud de ligandos peptídicos de la misma, para formar complejos de molécula MHC / ligando peptídico (pMHC), y c) cribado de dichos complejos moleculares pMHC según su unión a TCR.This is concerned with a method for ultra-rapid screening to identify a complex that binds to a TCR consisting of an MHC molecule and a peptide ligand, which comprises a stabilized MHC-peptide molecule and the respective uses of said method. The present also concerns polypeptides comprising or consisting of stabilized MHC molecules or peptide-binding fragments thereof, pharmaceutical compositions comprising said polypeptides, vaccines comprising said pharmaceutical composition and uses of said vaccine for the manufacture of a drug and / or for the prevention of cancer. The present also concerns nucleic acids encoding said polypeptides and vectors comprising said nucleic acids. Claim 1: Method for the screening of a complex that binds to a TCR formed by an MHC molecule and a peptide ligand (pMHC), comprising the following steps: a) providing a suitably stabilized MHC molecule, in which said molecule MHC comprises at least one artificially introduced covalent bridge: (I) between an amino acid of the a-1 domain and an amino acid of the a-2 domain of said stabilized MHC molecule in the case of MHC I; and / or (II) between two amino acids of the a-1 domain of said stabilized MHC molecule in the case of MHC I; or (III) between two amino acids of the a-1 domain or of the b-1 domain of said stabilized MHC molecule in the case of MHC II; and / or (IV) between one amino acid of domain a-1 and one amino acid of domain b-1 of said stabilized MHC molecule in the case of MHC II; b) contacting said suitably stabilized MHC molecule with a multitude of peptide ligands thereof, to form MHC molecule / peptide ligand (pMHC) complexes, and c) screening of said pMHC molecular complexes according to their binding to TCR.

ARP190102633A 2018-09-14 2019-09-13 METHOD FOR ULTRA-RAPID AFFINITY SCREENING OF MHC-PEPTIDE COMPLEXES IN SEARCH OF TCR LIGANDS AR114735A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201862731337P 2018-09-14 2018-09-14

Publications (1)

Publication Number Publication Date
AR114735A1 true AR114735A1 (en) 2020-10-07

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Family Applications (1)

Application Number Title Priority Date Filing Date
ARP190102633A AR114735A1 (en) 2018-09-14 2019-09-13 METHOD FOR ULTRA-RAPID AFFINITY SCREENING OF MHC-PEPTIDE COMPLEXES IN SEARCH OF TCR LIGANDS

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AR (1) AR114735A1 (en)

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