Model parameters. (RSE, Relative standard error)
| Parameter | Unit | Description | Value | RSE (%) | Comments and references |
|---|---|---|---|---|---|
| r | d−1 | Tumor growth rate | 0.4 | Taken from [41] | |
| TVmax | μL | Maximal size of tumor | 2500 | Taken from [41] | |
| d0 | d− 1 | Spontaneous death rate of tumor cells | 0.01 | Assumed and to preserve d0 < < r, given the proportion of apoptotic vs. proliferating cells is minor, in growing syngeneic tumors [25]. | |
| kLN | cells/d | Maximal influx rate of nTeff cells | 279 | 8 | Estimated based on tumor growth data |
| SL | n/a | T cell ability to infiltrate tumor tissue under systemic antigen exposure | 8.89 | 13 | Estimated based on tumor growth data |
| ΩSL | n/a | Random effects on kLN | 0.696 | 10 | Estimated based on tumor growth data |
| kpro | d−1 | nTeff proliferation rate constant | 3.0 | Estimated based on a minimal duration (6 h) of the cell division cycle [42] | |
| kdif | d−1 | nTeff differentiation rate constant | 3.2 | Assumed, to preserve observed nTeff/dTeff ratio in tumor tissue [43] | |
| kel | d−1 | nTeff elimination rate constant | 0.2 | Estimated based on half-life of primed T cells [42] | |
| kapo | d−1 | dTeff apoptosis rate constant | 2.0 | Estimated based on activated cytotoxic T cells in tissue [42] | |
| e | d− 1• cell− 1 | Rate of tumor cell kill by dTeff | 0.001 | Assumed based on CD8+ cell density in CT26, controlling tumor regrowth after RT [12, 25] | |
| Kpdl | cells | Sensitivity of PD-L1 expression up-regulation to dTeff count | 478 | 23 | Estimated based on tumor growth data |
| kpdl | d−1 | PD-L1 up-regulation rate constant | 1.0 | PD-L1 response was assumed to reach a steady-state in about 1 day, as shown in vitro [44] | |
| Ktcd | d− 1 | Sensitivity of DCm to TCD value | 0.2 | Assumed to be sufficiently high to stimulate DC maturation in the TME [17] | |
| SR | n/a | Sensitivity of cellular immuno-suppression to accumulation to systemic Ag level | 30.5 | 12 | Estimated based on tumor growth data |
| α | Gy− 1 | Linear component of radiation effect | 0.146 | 9 | Estimated based on tumor growth data |
| δ | Gy−1 | DSB formation per cell per Gy | 19 | Taken from [45] | |
| τ | d (day) | DSB repair time | 0.02 | Taken from [46] | |
| μ | d−1 | Elimination rate of radiation-damaged tumor cells | 0.1725 | Calculated from the half-life value [47] | |
| Vd | L | Volume of distribution for PD-L1 mAb i.p. PKPD model in mouse | 0.003 | Estimated from [48] | |
| ka | d−1 | i.p. absorption rate | 8.0 | Estimated from [48] | |
| kelmAB | d−1 | mAb elimination rate | 0.15 | Estimated from [48] | |
| KD | nM | mAb PD-L1(PD-1) binding affinity | 30 | Taken from internal data | |
| a | μL | Constant component of residual error | 21.2 | 13 | Estimated based on tumor growth data |
| b | n/a | Proportional component of residual error | 0.176 | 10 | Estimated based on tumor growth data |