Tapasin augmentation for enhanced immune response

An immune response and enhancer technology, applied in vaccines, medical preparations containing active ingredients, and the use of vectors to introduce foreign genetic material, etc., can solve the problems of reducing the expression of MHC molecules and the instability of MHC class I carrier complexes

Inactive Publication Date: 2011-08-17
塔皮穆内公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Defective expression of Tpn destabilizes the MHC class I transport complex includ

Method used

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  • Tapasin augmentation for enhanced immune response
  • Tapasin augmentation for enhanced immune response
  • Tapasin augmentation for enhanced immune response

Examples

Experimental program
Comparison scheme
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Embodiment Construction

[0014] The invention is now further illustrated in the following detailed examples, which are presented as illustrative only and should not be construed as otherwise limiting the scope or spirit of the invention or any embodiment thereof.

[0015] Materials and methods

[0016] Cells, Viruses, and Mice

[0017] HEK 293 cells (ATCC, Rockaway, MD, USA), CRE8 cells (S. Hardy (S. J.Virol; 71:1842-1849 (1997)), CMT.64 cells (Y.Lou et al.; Cancer Res.; 65 : 7926-7933 (2005)), CMT / VSV-NP (CMT.64 cells transfected with the VSV nucleocapsid protein (NP) minigene containing b Immunodominant epitope of amino acids 52 to 59 on ) and T1 (ATCC, CRL-1991, hTpn positive cell line). CRE8 cells have a β-actin-based expression cassette that utilizes an N-terminal nuclear localization signal to drive stable integration of the Cre recombinase gene into HEK 293 cells (S. Hardy et al., supra). The Ψ5 virus is an E1 and E3 deleted form of Ad5 containing loxP sites flanking the assembly site (S. H...

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Abstract

Tapasin (Tpn) is a member of the MHC Class I loading complex and functions to bridge the TAP peptide transporter to MHC Class I molecules. Metastatic human carcinomas express low levels of the antigen processing components (APCs) tapasin and TAP, and display few functional surface MHC Class I molecules. As a result, carcinomas are often unrecognizable by effector cytolytic T cells (CTLs). Tpn alone can enhance survival and immunity of mammals against tumors, but additionally, Tpn and TAP can be used together as components of immunotherapeutic vaccine protocols to eradicate tumors.

Description

Background technique [0001] The MHC class I antigen presentation pathway is essential for presentation to CD8 + T cells cross-present tumor antigens to elicit anti-tumor immune responses, and recognize and kill tumor cells through tumor-specific cytotoxic lymphocytes (CTLs) are of great significance. An important component of these two processes is the chaperone protein Tpn (Tpn), a 48 kDa type I membrane glycoprotein that functions to help transport antigenic peptides to class I in the endoplasmic reticulum (ER) molecularly. Mechanisms by which Tpn mediates this function include retention of empty MHC class I molecules in the ER until peptide loading, stabilization of transporters associated with antigen processing proteins (TAPs), bridging of MHC class I antigens to TAPs, and support of affinity peptides Binding to MHC class I antigens. In the presence of Tpn, surface MHC class I molecules are more stable and thus can more efficiently present antigen to CTLs or their prec...

Claims

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Application Information

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IPC IPC(8): A61K39/39A61P31/00A61P35/00A61P37/04A61K38/17A61K48/00A61K39/00
CPCA61K48/005A61K38/17A61K39/0011C12N2710/10343A61K48/00A61K2039/5156A61K2039/55516C12N15/86A61K2039/5152A61P31/00A61P31/04A61P31/06A61P31/12A61P31/14A61P31/16A61P31/20A61P35/00A61P35/02A61P37/04A61K2039/80
Inventor 威尔弗雷德·杰弗里斯
Owner 塔皮穆内公司
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