biostudies-literatureKerr CPNCI NIH HHSNIHNIGMS NIH HHSNIH HHSNIH NCI128https://www.ebi.ac.uk/biostudies/studies/S-EPMC9865370biostudies-literatureUnknown15(1)Targeted radionuclide therapy (TRT) and immunotherapy are rapidly growing classes of cancer treatments. Basic, translational, and clinical research are now investigating therapeutic combinations of these agents. In comparison to external beam radiation therapy (EBRT), TRT has the unique advantage of treating all disease sites following intravenous injection and selective tumor uptake and retention-a particularly beneficial property in metastatic disease settings. The therapeutic value of combining radiation therapy with immune checkpoint blockade to treat metastases has been demonstrated in preclinical studies, whereas results of clinical studies have been mixed. Several clinical trials combining TRT and immune checkpoint blockade have been initiated based on preclinical studies combining these with EBRT and/or TRT. Despite the interest in translation of TRT and immunotherapy combinations, many questions remain surrounding the mechanisms of interaction and the optimal approach to clinical implementation of these combinations. This review highlights the mechanisms of interaction between anti-tumor immunity and radiation therapy and the status of basic and translational research and clinical trials investigating combinations of TRT and immunotherapies.PharmaceuticsDevelopments in Combining Targeted Radionuclide Therapies and Immunotherapies for Cancer Treatment.PMC9865370F30CA268780T32 GM140935T32GM140935F30 CA268780P01CA250972Kerr CPWeichert JPGrudzinski JJHernandez RNguyen TPMorris ZSfalseDevelopments in Combining Targeted Radionuclide Therapies and Immunotherapies for Cancer Treatment.Targeted radionuclide therapy (TRT) and immunotherapy are rapidly growing classes of cancer treatments. Basic, translational, and clinical research are now investigating therapeutic combinations of these agents. In comparison to external beam radiation therapy (EBRT), TRT has the unique advantage of treating all disease sites following intravenous injection and selective tumor uptake and retention-a particularly beneficial property in metastatic disease settings. The therapeutic value of combining radiation therapy with immune checkpoint blockade to treat metastases has been demonstrated in preclinical studies, whereas results of clinical studies have been mixed. Several clinical trials combining TRT and immune checkpoint blockade have been initiated based on preclinical studies combining these with EBRT and/or TRT. Despite the interest in translation of TRT and immunotherapy combinations, many questions remain surrounding the mechanisms of interaction and the optimal approach to clinical implementation of these combinations. This review highlights the mechanisms of interaction between anti-tumor immunity and radiation therapy and the status of basic and translational research and clinical trials investigating combinations of TRT and immunotherapies.2022-01-01T00:00:00Z2022 Dec2024-11-05T15:14:39.247Z2024-11-05T15:14:39.247ZS-EPMC98653703667875610.3390/pharmaceutics15010128