Tumor xenografts as the model for a preclinical trials of genetically modified cell therapy
AbstractCurrently, anticancer therapy based on the adoptive transfer of genetically modified cells is being actively developed, which increasingly actualizes tumor xenografts as a model for preclinical testing of these cellular products. The tumor xenografts model is the closest of the existing methods that simulate natural tumor growth since it reproduces a three-dimensional vascularized tumor in the body with maintained homeostasis, metabolism, and possible mechanisms of tolerance to the therapeutic agent. Long-term use of the model has led to its standardization due to the emergence of well-characterized tumor cell lines and inbred mice, as well as in vivo imaging methods that measure the progression of cancer objectively. Modern approaches based on patient-derived tumor xenografts more closely imitate the intratumoral and intertumoral heterogeneity observed in clinical practice, which provides a more adequate assessment of the antitumor potential of the cell products studied. At the moment, the world literature has accumulated a large amount of data on the used tumor cell lines and inbred mice properties and the model methodology, which is necessary to obtain reliable results in the tumor xenograft model. The xenograft tumor biology and the interaction mechanisms of therapeutic genetically modified T cells and the tumor have been studied in sufficient detail, which will also be considered in this work to help in choosing an adequate and informative model for research.
Keywords:tumor xenografts; tumor cell lines; immunodeficient mice; genetically modified T-lymphocytes
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