KEY POINTS
- This preclinical study used CT26 colorectal tumors in mice to test whether external-beam radiotherapy could increase uptake and efficacy of PDL1-targeted radionuclide therapy using lutetium-177-labelled anti-PDL1 antibodies.
- A single 8 Gy radiotherapy fraction increased tumor-cell PDL1 expression, MHC-I expression, and lymphocyte infiltration. Six days later, irradiated tumors showed greater indium-111-labelled antibody uptake at 72 hours: 23.67 ± 2.79% versus 8.97 ± 0.90% injected dose per gram (p=0.0225).
- Lutetium-177-labelled anti-PDL1 at 3.3 or 7.8 MBq modestly delayed tumor growth, but combining it directly with radiotherapy did not significantly improve efficacy or survival over either treatment alone.
- High splenic antibody uptake was associated with lymphopenia and reduced intratumoral CD8-positive T-cell infiltration. Co-injection of a 15-fold excess of unlabelled anti-PDL1 reduced splenic uptake while preserving tumor targeting.
- Radiotherapy plus lutetium-177-labelled anti-PDL1 and antibody co-dosing produced two complete responses, prolonged survival, and prevented significant lymphopenia. Responding mice rejected tumor rechallenge at day 60.
CLINICAL TAKEAWAY
External-beam radiotherapy may prime colorectal tumors for PDL1-targeted radionuclide therapy by increasing target expression and immune infiltration. However, off-target splenic uptake can undermine efficacy and immune function, and the apparent benefit of antibody co-dosing remains preliminary evidence from a localized murine model.
SOURCE
International Journal of Radiation Oncology, Biology, Physics