摘要:
The invention relates to the field of immunology and immunotherapy, in particular, to adoptive T cell therapy of cancer utilizing T cell receptor (TCR)-engineered T cells. The invention provides novel methods and tools for identification and cloning of TCR, which are also applicable for identification of other receptors such as B cell receptors or antibodies. The invention provides immortalized cell lines able to induce subset specific (e.g. CD4 + or CD8 + specific) hybridization during co-culture, e.g., with primary lymphocytes of mice or men. The immortalized cells are engineered to express two mutated glycoproteins derived from the paramyxovirus family, namely hemagglutinin (H) and fusion (F) or a derivative thereof. H is a chimeric protein not able to bind to its natural ligands, fused to a targeting ligand capable of specifically binding to a specific cell surface antigen such as a lymphocytic subset-marking ligand (e.g. CD4 or CD8); fusion (F) mediates the fusion of cellular membranes of the immortalized cell line and cells, e.g., primary lymphocytes, H has bound to. The methods of the invention comprise preparing a hybridoma cell expressing a receptor, comprising steps of co-culturing a cell expressing a specific cell surface antigen and said receptor with the specific immortalized cells of the invention. The invention also relates to the hybridoma cells obtainable by said method.
摘要:
The present invention is directed to a functional T cell receptor (TCR) fusion protein (TFP) recognizing and binding to at least one MHC-presented epitope, and containing at least one amino acid sequence recognizing and binding an antigen. The present invention is further directed to an isolated nucleic acid molecule encoding the same, a T cell expressing said TFP, and a pharmaceutical composition for use in the treatment of diseases involving malignant cells expressing said tumor-associated antigen.
摘要:
The present invention relates to a method for selecting a host cell population expressing a functional fusion protein comprising at least one epitope-providing amino acid sequence (epitope-tag) and the amino acid sequence of a protein that is expressed on the surface of said host cell. Preferably, the amino acid sequence comprises an alpha or beta chain of a T-cell receptor. The present invention further relates to uses of said functional T-cell receptor (TCR) alpha or beta chain fusion protein in medicine, in particular in adoptive transfer.
摘要:
The present invention is directed to a functional T cell receptor (TCR) fusion protein (TFP) recognizing and binding to at least one MHC-presented epitope, and containing at least one amino acid sequence recognizing and binding an antigen. The present invention is further directed to an isolated nucleic acid molecule encoding the same, a T cell expressing said TFP, and a pharmaceutical composition for use in the treatment of diseases involving malignant cells expressing said tumor-associated antigen.
摘要:
The present invention relates to retroviral vector systems, in particular the development of packaging or helper cell lines that are based on T cells and that are suitable for producing T cell receptor retroviruses. Thereby, the present invention relates to T cell line specific retroviral expression vectors, and mammalian T cell line-based helper cell lines. The invention further relates to methods for expressing transgenes and to T cell line specific retroviral vector systems, including biochemical kits, that utilize and/or comprise the T cell line specific retroviral expression vectors and/or mammalian T cell line-based helper cell lines.