Table 2.
Population quantitative systems pharmacology model simulations of efficacy responses under various drug monotherapy and combination scenarios involving test antibodies against selected targets (PD‐L1, CTLA‐4, OX40, CXCR2) (fifth column) and a range of baseline conditions materialized in the model by different amounts of the different immune cell types (Teff, Treg, myeloid‐derived immuno‐suppressive cells, or MDSC) at the start of treatment (second to fourth columns), which are characteristic of the different types of syngeneic tumor models commonly used in IO preclinical research (first column)
| Tumor type | Teff | Treg | MDSC | Treatment | Efficacy, %responders |
|---|---|---|---|---|---|
| MCA205‐like | + | +/− | ++ | αPD‐L1 | 34 |
| αCXCR2 | 18 | ||||
| Rhabdomyosarcoma‐like | OX40L | 14 | |||
| αPD‐L1 + αCXCR2 | 94 | ||||
| αPD‐L1 + OX40L | 91 | ||||
| CT26‐like | + | ++ | +/− | αPD‐L1 | 0 |
| αCTLA‐4 | 0 | ||||
| αPD‐L1 + αCTLA‐4 | 98 | ||||
| αCTLA‐4 + OX40L | 6 | ||||
| αPD‐L1 + OX40L | 4 | ||||
| αPD‐L1 + αCXCR2 | 0 | ||||
| 4T1‐like | + | + | ++ | αCTLA‐4 | 0 |
| αPD‐L1 + αCTLA‐4 | 22 | ||||
| αPD‐L1 + OX40L | 0 | ||||
| αPD‐L1 + αCXCR2 | 0 | ||||
| αCTLA‐4 + αCXCR2 | 0 | ||||
| αPD‐L1 + αCTLA‐4 + αCXCR2 | 99 | ||||
| B16/F10‐like (poorly immunogenic) | +/− | +/− | + | αPD‐L1 + OX40L | 1 |
| αPD‐L1 + αCTLA‐4 | 9 | ||||
| αPD‐L1 + αCTLA‐4 + OX40L | 74 |
To derive an efficacy metric at cohort level (sixth column), we computed the percentage of responding animals in the cohort (%responders), “responder” being arbitrarily defined as an animal exhibiting a tumor volume < 100 mm3 at day 50 of the simulated treatment. IO, immuno‐oncology; MDSC, myeloid‐dervied suppressor cell; MCA205, mouse fibrosarcoma cell line; CT26, mouse colerectal carcinoma cell line; 4T1, mammary carcinoma; B16/F10, melonoma cell line