Table 1.
Combination of RT with Immunotherapy in Preclinical GBM Models
Immunotherapy Protocol | Preclinical Model | Outcome | Reference | |
---|---|---|---|---|
Combination of stereotactic RT protocol of 1 × 10 Gy on day 10 after tumor implantation with immune checkpoint antibodies | ||||
- mAb anti-PD1 (10 mg/kg) | - Orthotopic | - Increased mice survival | (Zeng et al. 2013) | |
- Concomittant then adjuvant | C57Bl/6 | - Reduced tumor growth | ||
- 4 doses, every 2 days | - 1.3 × 106 GL261luc | - 25% long survival | ||
- No tumor growth after rechallenge | ||||
- mAb anti-GITR (10 mg/kg) | - Orthotopic C57Bl/6 | - No survival advantage | (Patel et al. 2016) | |
- concomittant then adjuvant | - 1.3 × 106 GL261-luc | |||
- 3 doses, every 3 days | ||||
- mAb anti-PD1 (10 mg/kg) | - Orthotopic C57Bl/6 | - Increased mice survival | (Kim et al. 2017) | |
- Concomittant then adjuvant | - 1.3 × 106 GL261-luc | - Reduced tumor growth | ||
- 3 doses, every 2 days | - 60% long survival | |||
- Ab anti-TIM3 (10 mg/kg) | - Orthotopic C57Bl/6 | - Increased mice survival | (Kim et al. 2017) | |
- 3 doses on day 7, 11, 15 | - 1.3 × 106 GL261-luc | - Reduced tumor growth | ||
- 50% long survival | ||||
- Combination mAb anti-PD1 & Ab anti-TIM3 (both 10 mg/kg) | - Orthotopic C57Bl/6 | - Increased mice survival | (Kim et al. 2017) | |
- Concomittant then adjuvant | - 1.3 × 106 GL261-luc | - Reduced tumor growth | ||
- 100% long-survival | ||||
- Humanized Ab anti-CD47 | - Orthotopic NSG | - Increased mice survival | (Gholamin et al. 2020) | |
- Concomitant | - human primary cells | - Reduced tumor growth | ||
- Doses not indicated | ||||
- mAb anti-CTLA4 (8 mg/kg) | - Orthotopic C57Bl/6 | - Increased mice survival | (Belcaid et al. 2014) | |
- 3 doses (i.p.), day 11, 14, 17 | - 1.3 × 106 GL261-luc | - 20% long survival | ||
- Ab anti-4-1BB (24 mg/kg) | - Orthotopic C57Bl/6 | - No survival advantage | (Belcaid et al. 2014) | |
- 3 doses (i.p.), day 14, 17, 23 | - 1.3 × 106 GL261-luc | |||
- Combination mAb anti-CTLA4 (8 mg/kg) & anti-4-1BB (24 mg/kg) | - Orthotopic C57Bl/6 | - Increased mice survival | (Belcaid et al. 2014) | |
- 3 doses each (i.p.) on day 11, 14, 17, and 14, 17, 23 respectively | - 1.3 × 106 GL261-luc | - 50% long survival | ||
Combination of stereotactic RT protocol of 1 × 4 Gy on day 7 after tumor implantation with CAR T cells | ||||
- NKG2D-CAR T cells (5 × 106) | - Orthotopic C57Bl/6 | - Increased mice survival | (Weiss et al. 2018) | |
- 3 i.v. doses (day 5, 7, 10) | - 20 000 GL261-luc | - Decreased tumor growth | ||
- 20% long survival | ||||
- No tumor after tumor rechallenge | ||||
Combination of stereotactic RT protocol of 2 × 5 Gy on days 9 and 16 after tumor implantation with targeted nonviral nanoparticles | ||||
- Targeted nanoparticles containing PD-L1/EGFR si-RNAs (75ug/dose) | - Orthotopic C57Bl/6 | - Increased mice survival | (Erel-Akbaba et al. 2019) | |
- Retro-orbital injection | - 50 000 GL261-luc | |||
- 6 doses (day 12, 13, 15, 19, 20, 22) |