PD1-knockout chimeric antigen receptor T cell targeting DR5, preparation method and application thereof

Abstract

The invention provides a preparation method of a PD1-knockout chimeric antigen receptor T cell targeting DR5. The method comprises: linking an encoding gene of the chimeric antigen receptor CAR-DR5 and targeting DR5 to a vector, and constructing the recombinant lentivirus, performing transfection on CD3 positive T lymphocytes, and performing knockout of the PD1 gene of the transfected T cells to obtain the PD1-knockout chimeric antigen receptor T cell targeting DR5. The knockout of the PD1 gene is carried out by the chimeric antigen receptor T cell, which is in favor of amplification of T cells in the patient, and avoids the escape of immunosurveillance of the tumor cells, and the T cell has the performance of killing tumor cells with high efficiency and specificity, which maintains the viability and lethality of the cells for a long time and does not cause damage to normal cells.

Description

Technical field

[0001] The present invention relates to the field of medical biology, in particular to a chimeric antigen receptor T cell targeting DR5 that knocks out PD1, and a preparation method and application thereof. Background technique

[0002] Cancer has become the culprit threatening human life, and the incidence is on the rise. People started from the perspective of inducing tumor cell apoptosis or overcoming tumor cell tolerance to apoptosis, and discovered tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). ), is a member of the tumor necrosis factor superfamily that can induce apoptosis. Death receptor 5 (DR5) is a member of the tumor necrosis factor receptor superfamily (TN FRSF10B). Its cytoplasmic region contains a death domain, which is distributed in tumor cells, lymphatic tissues and activated T cells. TRAIL binds to DR5 on the cell surface and can induce cell apoptosis. DR5 is widely expressed in many solid tumor cells such as liver cancer, whi...

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