Novel cytokine-induced killer (CIK) cells for carrying cytokine loaded double-regulated oncolytic adenovirus

Abstract

The invention discloses novel CIK cells for carrying interleukin-2 (IL-2) loaded double-regulated oncolytic adenovirus and belongs to a method for preparing the novel CIK cells. The CIK cell can carry oncolytic adenovirus loaded with a cytokine such as (IL-2). After the oncolytic adenovirus is modified, an E1A promoter is replaced by a human telomerase reverse transcriptase (hTERT) promoter whileE1B55-kD is deleted from the shuttle plasmid of the oncolytic adenovirus, and thus, the double regulation of the selective propagation of the oncolytic adenovirus in tumor cells are realized. Then, the shuttle plasmid is recombined with the skeleton plasmid pBHG-fiber5 / 35 of adenovirus to form the chimeric dynein structure of the coat of the oncolytic adenovirus, so that the ability of infecting the CIK cells by the oncolytic adenovirus is improved. After the CIK cells enter a body and kill tumor cells, the released oncolytic adenovirus can play a secondary tumor cell killing effect, the secreted cytokine IL-2, at the same time, can improve the antitumor ability of the CIK cells, and thus, a 'cell-virus-gene' synergetic antitumor effect is achieved. The CIK cells also reduce the side effects of whole body cytokines and the oncolytic adenovirus.

Description

technical field [0001] The invention relates to the fields of genetic engineering and tumor biotherapy. Specifically, the present invention relates to the use of gene mutation and recombination techniques to delete the viral E1B55-kD protein, regulate the expression of the viral E1A protein, and transform the ciliary protein of the oncolytic adenovirus, so as to improve the ability of the oncolytic adenovirus to target and infect CIK cells and security. At the same time, the therapeutic gene IL-2 is inserted into the oncolytic adenovirus, and the dual-regulated oncolytic adenovirus loaded with IL-2 is carried to the tumor tissue site through CIK cells, and the synergistic killing of tumor by CIK cells, oncolytic adenovirus and cytokines is exerted The effect, while enhancing the targeted anti-tumor effect, avoids the side effects of systemic application. Background technique [0002] Oncolytic adenovirus, as a special tumor therapy drug and gene therapy carrier, has develo...

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