1/12/2023 0 Comments Nod scid gammaImmunotherapy, which has rapidly become a cornerstone of melanoma treatment, cannot be modeled with current PDX melanoma approaches. However, this strength is also a limitation in light of the increasingly recognized importance of cell-extrinsic mechanisms, such as antitumor immunity, in determining patient outcomes-even outcomes to treatment with agents that target cell intrinsic disease drivers (ie, mutated BRAF 95). Indeed, a major advantage of using PDX melanomas is their facilitation of study of cell-intrinsic determinants of disease biology and therapy response/resistance, which in immunocompromised mice may be substantially uncoupled from cell-extrinsic effects such as immune regulation of disease. These properties encourage use of PDX melanomas for examining mechanisms through which melanomas adapt and evolve during disease progression and in the face of therapy. This heterogeneity can be maintained or even increased during propagation of PDX lines due to continued genomic instability, as is seen in patients. Moreover, there is a relatively low degree of selection in PDX melanomas of cells with tumor-forming potential in patients, meaning that the heterogeneity of patient tumors is well represented. This means that only small numbers of cells are necessary to first establish a PDX line, and that only very few patient melanomas cannot be established as PDX tumors. Modern PDX melanoma assays in NSG mice are more efficient than PDX assays described for most other cancers, as tumor formation can be generated from very high proportions (25–30% on average) of transplanted cells. Shackleton, in Patient Derived Tumor Xenograft Models, 2017 Future/Challenges Transgenic mice have been used in neuroAIDS studies to characterize the mechanism of HIV-induced neurotoxicity that may be implemented in HAND. Both HIV-infected and immune-activated macrophages in the CNS release neurotoxins that can induce apoptosis and damage dendrite and synapse function ( Rahimian and He, 2016). NeuroAIDS studies using humanized mice highlighted the importance of Mo/MΦ infection and their association with neuronal injury in the development of HIV-associated encephalitis ( Gorantla et al., 2010 Dash et al., 2011 Honeycutt et al., 2016). This important study underscores the pivotal role of macrophages in AIDS and HIV-associated CNS pathology ( Honeycutt et al., 2016). A recent study using this model, termed the “macrophage-only mice,” demonstrated that Mo/MΦs alone can sustain HIV infection in the absence of CD4 + T cells. NSG mice that are transplanted with human hematopoietic stem cells or BM without human thymus and liver tissue will develop mature human myeloid, but not lymphoid, cells ( Honeycutt et al., 2016). NSG mice are a useful model for studying specific immune responses and infected cells implicated in HIV-associated neuropathogenesis ( Sun et al., 2007 Lavender et al., 2013). Williams, in Handbook of Clinical Neurology, 2018 T-cell and macrophage-only humanized mice Animals bearing the Raji cells were subsequently randomized into different groups with half males and half females according to their body weights or fluorescence intensity. If a Raji cell with fluorescence reporter was used, the fluorescence intensity of animals for the proliferation of the lymphoma could be detected 72–96 h after xenografting using IVIS Lumina III (Perkin Elmer). Before the study was conducted, mice were quarantined for 5 days.Īnimals to be administrated with CAR-T were intravenously dosed with 0.2 mL Raji cells (3 ~ 5 × 10 5 cells per animal) for tumor xenografts in advance. Animals had ad libitum access to certified rodent diet, and sterilized municipal tap water was given ad libitum via water bottles. Six-week-old specific pathogen free (SPF) NSG mice were housed in individually ventilated cages in a barrier system under conditions of 20–26 ☌, 40–70% relative humidity, a 12-h light–dark cycle, and a cage air exchange of over 50 times per hour. NSG mice with IL2rg gene knockout and NOD- scid genetic background, lacking mature T, B and NK cells, are recognized as a suitable immunodeficient model for the cell xenografting. Yan Huo, in Methods in Cell Biology, 2022 2.2 Animals and tumor xenografting
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