FIELD: biotechnology.
SUBSTANCE: disclosed is a constitutively active chimeric cytokine receptor (CACCR) for increasing the cytotoxicity of an engineered immune cell, wherein the CACCR consists of two monomers, where each monomer contains: a thrombopoietin receptor (TpoR) transmembrane domain containing amino acids 478–582 of SEQ ID NO: 6 with amino acid substitutions S505N and W515K according to SEQ ID NO: 6, a domain which binds Janus kinase (JAK) and an intracellular STAT recruiting domain. Also disclosed are: a polynucleotide coding CACCR, an expression vector, engineered T-cells having increased cytotoxicity and a method for production thereof, a pharmaceutical composition and a kit for treating cancer in a subject. Also disclosed is the use of a therapeutically effective amount of engineered T-cells or a pharmaceutical composition for treating cancer in a subject.
EFFECT: invention provides increased activation, proliferation, resistance and/or activity of immune cells and is used for treating cancer in a subject, in particular for treating a solid tumor or haemablastosis.
45 cl, 23 dwg, 8 tbl, 12 ex
| Title | Year | Author | Number |
|---|---|---|---|
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|
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| CHIMERIC CYTOKINE RECEPTOR | 2016 |
|
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| TRANSGENIC GENETIC LABELS AND METHODS OF USE | 2015 |
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| EXPRESSION OF NEW CELL MARKS | 2018 |
|
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| MAT-DIRECTED CHIMERIC ANTIGEN RECEPTOR SYSTEMS FOR SORTING/DEPLETING THE ENGINEERED IMMUNE CELLS | 2016 |
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| METHODS AND COMPOSITIONS FOR TRANSDUCTION AND EXPANSION OF LYMPHOCYTES AND REGULATION OF ACTIVITY THEREOF | 2018 |
|
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| CELL | 2016 |
|
RU2729158C2 |
| CHIMERIC RECEPTORS CONTAINING TRAF-6-INDUCING DOMAINS AND COMPOSITIONS AND METHODS RELATED TO THEM | 2016 |
|
RU2773159C2 |
