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Table 1 Preclinical studies demonstrating antitumor activity of combined radiation therapy and PD-1/PD-L1 blockade

From: Radiation therapy and PD-1/PD-L1 blockade: the clinical development of an evolving anticancer combination

Cell line Experimental model RT dose PD-1/PD-L1 dose Ref.
B16-D5 (melanoma) Mice subcutaneous TBI 600 cGy (1 fraction) PD-L1 mAb 20 mg/kg IP starting on day 4 then every 3–4 days +1X106 gp100 or OVA257–264 pulsed dendritic cell vaccine SC on day 4 and 11 ± 1X107 pmel T-cells (adoptive transfer) IV on day 4 after inoculation [69]
AT.3 (triple-negative mammary) Mice xenograft 12 Gy (1 fraction) or 4–5 Gy (4 fractions) PD-1 mAb 100 μg + CD137 mAb 100 μg IP on days 0, 4, 8, and 12 of RT [70, 71]
GL261 (glioma) Mice xenograft 10 Gy (1 fraction) PD-1 mAb 10 mg/kg IP on days 10, 12, and 14 of RT [72]
B16-SIY (melanoma) TUBO (mammary) Mice subcutaneous 25 Gy (2 fractions) 15 Gy (1 fraction) PD-L1 mAb 200 μg IP every 3 days for 4 doses starting 3 weeks after RT [92]
5 T33 (myeloma)
A20 (B-cell lymphoma)
C1498 (leukemia)
Mice intravenous TBI 500 cGy (1 fraction) PD-L1 mAb 200 μg IP on days 12, 14, 17, 19, 21, 26, and 28 after inoculation [75]
5 T33 (myeloma) Mice intravenous TBI 1100 cGy (1 fraction) HSCT on day 0 + PD-L1 mAb 200 μg IP on days 3, 5, 10, 12, 17, and 19 after HSCT ± vaccine (irradiated 5 T33 cells or 5 T33 cells transfected with empty vectors) on days 3, 10, and 17 after HSCT [73]
5 T33 (myeloma) Mice intravenous TBI 500 cGy (1 fraction) PD-L1 mAb 200 μg IP on days 12, 14, 17, 19, 21, 26, and 28 after inoculation ± LAG-3, TIM-3, or CTLA-4 mAbs 200 μg IP on same days [74]
CT26 (colon 4434 (BRAFV600E-mutant melanoma)
4 T1 (triple-negative mammary)
Mice subcutaneous 10 Gy (5 fractions) PD-1 or PD-L1 mAb 10 mg/kg IP 3 times weekly up to 3 weeks starting on day 1 of RT [86]
TUBO (mammary)
MC38 (colon
Mice subcutaneous 12 Gy (1 fraction) PD-L1 mAb 200 μg IP every 3 days for 4 doses starting on day 0 or 1 of RT [76]
TSA (mammary) Mice subcutaneous 24 Gy (3 fractions) PD-1 mAb (dose NR) starting on day 15 after inoculation and every 4 days thereafter [77]
B16-OVA (melanoma)
RENCA (renal)
Mice subcutaneous 15 Gy (1 fraction) PD-1 mAb 10 mg/kg ± CTLA-4 mAb 10 mg/kg IP on days 7, 9, 11, 14, and 16 following tumor cell inoculation [87]
B16-OVA (melanoma)
4 T1-HA (mammary)
Mice subcutaneous 12 Gy (1 fraction) PD-1 mAb 200 μg IP every 3 days for 3 doses starting 1 day prior to RT [79]
PyMT (mammary) Mice subcutaneous 12 Gy (1 fraction) PD-1 mAb dose NR + single dose of CTLA-4 mAb (dose NR) 3 days prior to PD-1 and RT [78]
B16-F10 (melanoma) Mice subcutaneous 20 Gy (1 fraction) PD-L1 mAb 200 μg + CTLA-4 mAb 200 μg IP every 3 days for 3 doses starting 5 or 9 days after inoculation [61]
Meer (head and neck squamous) Mice subcutaneous 1, 6, 10 Gy fractions PD-L1 antibody dose NR [82]
Adeno-Cre viral vector (lung) GEMM intrathoracic injection 8.5 Gy twice daily over 2 days PD-1 mAb 200 μg IP 3 times weekly starting 6 h after second RT dose [81]
MB49 (bladder) Mice xenograft 12 Gy (1 fraction) PD-L1 mAb 250 μg IP twice weekly for 4 doses starting 1 day prior to RT [84]
MC38 (colon
4 T1 (mammary) B16F10-OVA (melanoma)
Mice subcutaneous 24 Gy (3 fractions) PD-1 mAb ± CD137 mAb 5–10 mg/kg IP on days 13, 15, and 17 after inoculation [83]
4-hydroxytamoxifen induction (BRAF-mutant, PTEN-deficient melanoma) GEMM topical induction 14 Gy (1 fraction) PD-1 + CD137 or PD-1 + CTLA-4 mAb 100 μg IP twice weekly for 4 doses on day 1 of RT [99]
344SQ (lung) Mice subcutaneous 36 Gy (3 fractions) PD-1 mAb 10 mg/kg IP starting on day 1 of RT and continued for additional 3–4 doses [91]
ARK (esophageal squamous) Mice subcutaneous 20 Gy (10 fractions) PD-1 mAb (dose NR) starting 2 days before RT and every 3 days thereafter ± carboplatin and paclitaxel IP (dose NR) on day 1 of RT and every 3 fractions [85]
GL261 (glioma) Mice xenograft 10 Gy (1 fraction) PD-1 mAb 200 μg IP on days 10, 12, and 14 of RT ± TIM-3 mAb 250 μg IP days 7, 11, and 15 of RT [90]
CT26 (colon 4434 (BRAFV600E-mutant melanoma) Mice subcutaneous 10 Gy (5 fractions) PD-1 or PD-L1 mAb 10 mg/kg IP 3 times weekly for 1 week starting on day 1 of RT [88]
TSA (mammary) Mice subcutaneous 24 Gy (3 fractions) on days 12, 13 and 14 after inoculation PD-1 mAb 200 μg IP on days 12, 15, 19, 22 and 26 after inoculation [89]
Hep-55.1c (hepatocellular) Mice orthotopic 30 Gy (3 fractions) PD-1 mAb 250 μg IP on days 7, 14, and 21 after inoculation [96]
KPC and Pan02 (pancreatic) Mice subcutaneous 6, 12, or 20 Gy (1 fraction)
10 Gy (5 fractions)
15 Gy (5 fractions)
PD-L1 mAb 10 mg/kg IP on days 4, 7, 10, and 13 after inoculation + gemcitabine 100 mg/kg IP on days 0 and 3 of inoculation [95]
HCa-1 (hepatocellular) Mice intramuscular 10 Gy (1 fraction) PD-L1 mAb 10 mg/kg IP every 3 days for 4 doses starting on day 1 of RT [97]
LM8 (osteosarcoma) Mice subcutaneous 10 Gy (1 fraction) PD-L1 mAb 150 μg + CTLA-4 mAb 150 μg IP every 3 days for 3 doses starting on days 9, 12, and 15 after inoculation [98]
CT26 (colon Mice intradermal RFA 17-gauge single ablation electrode for 3.5–4.5 min at target temperature of 70 degrees C PD-1 mAb 200 μg IP every 3 days for 4 doses [94]
  1. RT radiation therapy, TBI total body irradiation, cGy centigray mAb monoclonal antibody, IP intraperitoneal, SC subcutaneous, IV intravenous, Gy Gray, HSCT hematopoietic stem cell transplantation, LAG-3 lymphocyte-activation gene 3, TIM-3 T-cell immunoglobulin mucin-3, NR not reported, GEMM genetically engineered mouse model, RFA radiofrequency ablation