The invention belongs to the technical field of
gene engineering, and particularly relates to a
pleural mesothelioma animal model construction method and application capable of simulating
immunotherapy response, and the method comprises the following steps: culturing human or
mouse lung cells into a first organ, carrying out TrypLE resuspension
digestion into single cells, carrying out genetic modification, and culturing into a second organ; the genetic modification is one of the following
modes: I, knocking out Trp53,
Pten, Cdkn2a and Cdkn2b genes, and overexpressing a Sox2
mutant gene and a Myc
gene; and II, knocking out the Trp53 gene, the
Pten gene, the Cdkn2a gene, the Cdkn2b gene and the Bap1 gene, and carrying out overexpression on the Sox2
mutant gene and the Myc gene. Resuspending and digesting the second organ to prepare a
cell suspension; and injecting the mixture between the dirty layer pleura of the mouse, and culturing for 90-120 days to construct the
pleural mesothelioma mouse model. Compared with a transplanted tumor
animal model, the method has the advantages that the
animal model keeps a natural microenvironment for tumor generation and development in an
animal body, and the accuracy is higher in the aspect of simulating real clinical patient conditions.