Modelling the efficacy of CAR-CIK cell immunotherapy targeting MET-expressing mesothelioma cells

Malignant pleural mesothelioma (MPM) is an aggressive tumour associated with poor prognosis and limited treatment options, motivating the investigation of novel therapeutic approaches. Among these, chimeric antigen receptor (CAR)–based adoptive cell therapy has attracted considerable interest given its potential to achieve durable clinical responses. In this paper, we combine experimental and mathematical approaches to investigate the efficacy of a CAR-based immunotherapy using cytokine-induced killer (CIK) cells engineered with a MET-specific receptor targeting MET-expressing tumour cells. In vitro data from diverse MPM cell lines and CIK preparations are used to develop and calibrate a mathematical model describing the interaction dynamics between tumour cells, structured by their MET expression level, and CIK cells. The model successfully reproduces experimental observations and is used to predict treatment efficacy under previously untested conditions, which are validated with new data from MPM primary cell lines, supporting the robustness of the mathematical framework. Our results elucidate the interplay between three key factors positively impacting treatment efficacy: the initial immune-to-tumour cell ratio, the percentage of CAR-MET-expressing CIK cells generated upon engineering, and the MET expression level of tumour cells. Together, these findings provide a quantitative basis for assessing CAR-CIK therapy effectiveness, which supports clinical decision making.