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Updated: Jan 13, 2026

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
Published on: January 29, 2019
Unlocking the therapeutic potential of immuno-radiotherapy: insights from preclinical and clinical research
M M Cogels1,2, A de Caluwé1,3, L Buisseret3,4
1Department of Radiotherapy, Institut Jules Bordet, Hopital Universitaire de Bruxelles (HUB), Brussels, Belgium.
The immunomodulatory potential of radiotherapy provides a strong rationale for its combination with immunotherapies and other immunostimulatory agents. However, current combinations yield suboptimal clinical benefits. As the mechanisms behind radiotherapy-induced immunomodulation are gradually unraveled, various key factors have been identified as critical modulators of this process, opening new possibilities for adapting radiotherapy to immunotherapy. Here, we discuss seven factors: dose‒fractionation regimens of radiotherapy (RT), sequence and timing of RT and immunotherapy, radiation field, type of ionizing radiation, normal tissue effects, choice of the lesion to irradiate and identification of biomarkers. Preclinical and clinical studies on the combination of immunotherapy and radiotherapy are discussed, novel immunotherapeutic approaches are highlighted and improvements in study design are suggested.
The immunomodulatory potential of radiotherapy provides a strong rationale for its combination with immunotherapies and other immunostimulatory agents. However, current combinations yield suboptimal clinical benefits. As the mechanisms behind radiotherapy-induced immunomodulation are gradually unraveled, various key factors have been identified as critical modulators of this process, opening new possibilities for adapting radiotherapy to immunotherapy. Here, we discuss seven factors: dose‒fractionation regimens of radiotherapy (RT), sequence and timing of RT and immunotherapy, radiation field, type of ionizing radiation, normal tissue effects, choice of the lesion to irradiate and identification of biomarkers. Preclinical and clinical studies on the combination of immunotherapy and radiotherapy are discussed, novel immunotherapeutic approaches are highlighted and improvements in study design are suggested.
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