Product name
Site-directed mutagenesis of T-cell receptorsSummary
human T-cells with tumor antigen-specific T-cell receptors so as to increase specific recognition of tumor antigens and lysis of target and malignant cellsOrganization name
IMG Innovations-Management GmbHProfile
The hereinafter specified innovation constitutes a novel genetic technique in the area of applied immunology and oncology. With that approach we were able to harness human T-cells with tumor antigen-specific T-cell receptors (TCR) so as to increase specific recognition of tumor antigens and lysis of target and malignant cells.
The T-cell receptor exclusively recognizes the antigen as a TCRαβ heterodimer. Applying rational design based on empirical TCR structures we identified pairs of interacting residues at the interface that selectively determine pairing of the relevant TCR chains. Endogenous host TCR chains are expelled from forming hybrid heterodimeric TCRs of unknown specificity, at the worst with autoimmune reactivity. Specific functionality and stability of the recombinant TCR is maintained. The modifications have been introduced into common domains of the TCR so as to yield therapeutic molecules irrespective of their species, family and antigen-specificity.
Application
This innovation could be used as an operation for the biochemical synthesis of gene-modified antigen-specific T-lymphocytes with clinical relevance for example tumor-/virus - antigens. Also it offers a new approach for immune therapy, for diagnosis and prevention/ prophylaxis of cancer. Prospective clinical setting could be: Peripheral T-cells of a tumor patient are isolated, gene-transferred with the designated modified tumor antigen-specific TCR, expanded ex vivo and reinfused (adoptive T-cell transfer).
Advantages
- Both individual and general tumor therapy applicable
- Preferential interaction of the exogenous TCRαβ chains and thereby stabilisation through dimerisation: increase of surface expression of the therapeutic molecule
- Formation of hybrid TCRs avoided: risk for the raise of autoimmune reactions averted
- Functionality and stability of the recombinant protein preserved
- Antigenicity and rejection of the modified therapeutic molecule minimised
Stage of Development
- Modified murine TCRs specific for the human onco-protein MDM2 or p53 and human TCRs specific for human gp100 have been successfully tested
Contact
IMG Innovations-Management GmbH
Antje Deichmann
deichmann(at)img-rlp.de
About IMG
The IMG Innovations-Management GmbH is a subsidiary of the Investment and Economic Development Bank of Rhineland-Palatinate GmbH. It offers a multitude of services for the realisation and commercialisation of innovations and inventions including intellectual property protection and license brokerage. It is the primary contact point regarding all matters of technology and knowledge transfer within the German state of Rhineland-Palatinate. Within the framework of the Scientific Patent Network Rhineland-Palatinate it forms the connection between scientists and university administrations and provides universities and research institutions with all prerequisites to bring research results to the market on a fast track. Within the Scientific Patent Network the IMG is the leading service provider offering as a proficient partner a professional intellectual property management to all associated universities and institutions.
Description File
umz003_t_cell_recepea31caac.pdf
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