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 nT
eff
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 k
LN
|
0.696
|
10
|
Estimated based on tumor growth data
|
kpro
|
d−1
|
nT
eff
proliferation rate constant
|
3.0
| |
Estimated based on a minimal duration (6 h) of the cell division cycle [42]
|
kdif
|
d−1
|
nT
eff
differentiation rate constant
|
3.2
| |
Assumed, to preserve observed nTeff/dTeff ratio in tumor tissue [43]
|
kel
|
d−1
|
nT
eff
elimination rate constant
|
0.2
| |
Estimated based on half-life of primed T cells [42]
|
kapo
|
d−1
|
dT
eff
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 dT
eff
|
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 dT
eff
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 DC
m
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
|