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FIGURE 2 | Schematic diagram of human <t>QSP</t> model. Human QSP model was built by combining the reported model of Wang et al. [33] and a por- tion of oncolytic virus mechanism of action in the preclinical QSP model shown in Figure 1. APC, antigen-presenting cell; Arg-1, arginase 1; aTCD8, activated CD8-positive T cells; CCL-2, chemokine (C-C motif) ligand 2; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; e, rate of tumor-cell kill by differentiated effector T cells; IL-2, interleukin 2; IL-7, interleukin 7; IL-12, interleukin 12; mAPC, MHC-presenting APC; MDSC, myeloid- derived suppressor cells; MHC, major histocompatibility complex; nTCD4, naïve CD4-positive T cells; nTCD8, naïve CD8-positive T cells; NO, nitric oxide; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; QSP, quantitative systems pharmacology; TCR, T-cell receptor; Teff, effector T cells; Treg, regulatory T cells; Tumi, infected tumor cells; Tumni, noninfected tumor cells; Valpha, viral production size.
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FIGURE 2 | Schematic diagram of human <t>QSP</t> model. Human QSP model was built by combining the reported model of Wang et al. [33] and a por- tion of oncolytic virus mechanism of action in the preclinical QSP model shown in Figure 1. APC, antigen-presenting cell; Arg-1, arginase 1; aTCD8, activated CD8-positive T cells; CCL-2, chemokine (C-C motif) ligand 2; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; e, rate of tumor-cell kill by differentiated effector T cells; IL-2, interleukin 2; IL-7, interleukin 7; IL-12, interleukin 12; mAPC, MHC-presenting APC; MDSC, myeloid- derived suppressor cells; MHC, major histocompatibility complex; nTCD4, naïve CD4-positive T cells; nTCD8, naïve CD8-positive T cells; NO, nitric oxide; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; QSP, quantitative systems pharmacology; TCR, T-cell receptor; Teff, effector T cells; Treg, regulatory T cells; Tumi, infected tumor cells; Tumni, noninfected tumor cells; Valpha, viral production size.
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FIGURE 2 | Schematic diagram of human <t>QSP</t> model. Human QSP model was built by combining the reported model of Wang et al. [33] and a por- tion of oncolytic virus mechanism of action in the preclinical QSP model shown in Figure 1. APC, antigen-presenting cell; Arg-1, arginase 1; aTCD8, activated CD8-positive T cells; CCL-2, chemokine (C-C motif) ligand 2; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; e, rate of tumor-cell kill by differentiated effector T cells; IL-2, interleukin 2; IL-7, interleukin 7; IL-12, interleukin 12; mAPC, MHC-presenting APC; MDSC, myeloid- derived suppressor cells; MHC, major histocompatibility complex; nTCD4, naïve CD4-positive T cells; nTCD8, naïve CD8-positive T cells; NO, nitric oxide; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; QSP, quantitative systems pharmacology; TCR, T-cell receptor; Teff, effector T cells; Treg, regulatory T cells; Tumi, infected tumor cells; Tumni, noninfected tumor cells; Valpha, viral production size.
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FIGURE 2 | Schematic diagram of human <t>QSP</t> model. Human QSP model was built by combining the reported model of Wang et al. [33] and a por- tion of oncolytic virus mechanism of action in the preclinical QSP model shown in Figure 1. APC, antigen-presenting cell; Arg-1, arginase 1; aTCD8, activated CD8-positive T cells; CCL-2, chemokine (C-C motif) ligand 2; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; e, rate of tumor-cell kill by differentiated effector T cells; IL-2, interleukin 2; IL-7, interleukin 7; IL-12, interleukin 12; mAPC, MHC-presenting APC; MDSC, myeloid- derived suppressor cells; MHC, major histocompatibility complex; nTCD4, naïve CD4-positive T cells; nTCD8, naïve CD8-positive T cells; NO, nitric oxide; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; QSP, quantitative systems pharmacology; TCR, T-cell receptor; Teff, effector T cells; Treg, regulatory T cells; Tumi, infected tumor cells; Tumni, noninfected tumor cells; Valpha, viral production size.
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FIGURE 2 | Schematic diagram of human <t>QSP</t> model. Human QSP model was built by combining the reported model of Wang et al. [33] and a por- tion of oncolytic virus mechanism of action in the preclinical QSP model shown in Figure 1. APC, antigen-presenting cell; Arg-1, arginase 1; aTCD8, activated CD8-positive T cells; CCL-2, chemokine (C-C motif) ligand 2; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; e, rate of tumor-cell kill by differentiated effector T cells; IL-2, interleukin 2; IL-7, interleukin 7; IL-12, interleukin 12; mAPC, MHC-presenting APC; MDSC, myeloid- derived suppressor cells; MHC, major histocompatibility complex; nTCD4, naïve CD4-positive T cells; nTCD8, naïve CD8-positive T cells; NO, nitric oxide; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; QSP, quantitative systems pharmacology; TCR, T-cell receptor; Teff, effector T cells; Treg, regulatory T cells; Tumi, infected tumor cells; Tumni, noninfected tumor cells; Valpha, viral production size.
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FIGURE 2 | Schematic diagram of human QSP model. Human QSP model was built by combining the reported model of Wang et al. [33] and a por- tion of oncolytic virus mechanism of action in the preclinical QSP model shown in Figure 1. APC, antigen-presenting cell; Arg-1, arginase 1; aTCD8, activated CD8-positive T cells; CCL-2, chemokine (C-C motif) ligand 2; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; e, rate of tumor-cell kill by differentiated effector T cells; IL-2, interleukin 2; IL-7, interleukin 7; IL-12, interleukin 12; mAPC, MHC-presenting APC; MDSC, myeloid- derived suppressor cells; MHC, major histocompatibility complex; nTCD4, naïve CD4-positive T cells; nTCD8, naïve CD8-positive T cells; NO, nitric oxide; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; QSP, quantitative systems pharmacology; TCR, T-cell receptor; Teff, effector T cells; Treg, regulatory T cells; Tumi, infected tumor cells; Tumni, noninfected tumor cells; Valpha, viral production size.

Journal: CPT: pharmacometrics & systems pharmacology

Article Title: A Multiple-Model-Informed Drug-Development Approach for Optimal Regimen Selection of an Oncolytic Virus in Combination With Pembrolizumab.

doi: 10.1002/psp4.13297

Figure Lengend Snippet: FIGURE 2 | Schematic diagram of human QSP model. Human QSP model was built by combining the reported model of Wang et al. [33] and a por- tion of oncolytic virus mechanism of action in the preclinical QSP model shown in Figure 1. APC, antigen-presenting cell; Arg-1, arginase 1; aTCD8, activated CD8-positive T cells; CCL-2, chemokine (C-C motif) ligand 2; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; e, rate of tumor-cell kill by differentiated effector T cells; IL-2, interleukin 2; IL-7, interleukin 7; IL-12, interleukin 12; mAPC, MHC-presenting APC; MDSC, myeloid- derived suppressor cells; MHC, major histocompatibility complex; nTCD4, naïve CD4-positive T cells; nTCD8, naïve CD8-positive T cells; NO, nitric oxide; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; QSP, quantitative systems pharmacology; TCR, T-cell receptor; Teff, effector T cells; Treg, regulatory T cells; Tumi, infected tumor cells; Tumni, noninfected tumor cells; Valpha, viral production size.

Article Snippet: Clinical QSP model Clinical ABM Software MATLAB, SimBiology Virtual Tumour (coded in MATLAB) Number of equations 160 67 Number of species 124 34 Number of parameters 185 47 Time to run Approximately 2 h Around 90 s per individual simulation (overall run time depends on the number of individual simulations required) Output No clear difference was observed.

Techniques: Virus, Derivative Assay, Immunopeptidomics, Infection