A Mathematical Model Of Adoptive Cell Immunotherapy For Melanoma

Adoptive cell immunotherapy(ACT)refers to the isolation of immunocompetent cells from tumor patients,in vitro expansion and functional identification,and then reinfusion to patients,so as to directly kill tumors or stimulate the body's immune response to kill tumor cells.Each type of tumor cell has its own unique mechanism against immune therapy.For melanoma cells,immunotherapy can be escaped by changing the phenotype in the treatment environment,that is,changing from a differentiated phenotype to a dedifferentiated phenotype mediated by the proinflammatory factor TNF-?.This article mainly considers the model of melanoma skin cancer cells under adoptive T cell therapy.The first chapter briefly introduces the immune escape mechanism and the biological background of the immune escape mechanism of melanoma skin cancer observed in clinical experiments,the research status of immune escape and adoptive cell immunotherapy mathematical models,and the basic concepts and theories of ordinary differential equations.Chapter 2 discusses adoptive cell immunotherapy for melanoma cells using a single type of T cells with or without constant input.A four-dimensional dynamic ordinary differential equation system for the exchange of substances between differentiated melanoma skin cancer cells,dedifferentiated melanoma cancer cells,a single type of T cells,and the proinflammatory factor TNF-? was established.We analyzed the existence and stability conditions of the non-negative equilibrium point of the system.Finally,given a set of biologically meaningful parameters,we studied the effects of changes in the constant input rate of the T cell and cancer-related parameters of the dedifferentiated phenotype on system dynamics through numerical simulation.Based on the previous chapter,the third chapter builds an adoptive cell immunotherapy model for treating melanoma skin cancer with two specific T cells,and mathematically tests this new treatment method.We have established a five-dimensional ordinary differential equation system for substance exchange between differentiated melanoma skin cancer cells,dedifferentiated melanoma cancer cells,two types of T cells,and the proinflammatory factor TNF-?.And we analyzed the dynamic behavior of the system,and the final result showed that compared with the treatment method in Chapter 2,the number of tumors to reach a stable state,the range of available parameters is wider,and it is easier under the current medical level conditions achieve.At the same time,we verified the importance of the T cell input rate for killing tumor cells,and provided a method feasibility prediction for the treatment of melanoma cells.The last chapter summarizes the research results of this article and introduces the direction of future research work.