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A bispecific single-domain antibody-Fc fusion protein, KN046, exhibits a good treatment effect by binding to programmed cell death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). An ionizing-radiation stimulus mediated by a low-dose of [\n                      <jats:sup>131<\/jats:sup>\n                      I] may be used for immunopotentiation. In this study, we established [\n                      <jats:sup>131<\/jats:sup>\n                      I]-labeled KN046 as a novel radioimmunotherapy agent to treat malignant melanoma and explored the mechanism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      After\u00a0intravenous\u00a0injection\u00a0of [\n                      <jats:sup>131<\/jats:sup>\n                      I]-KN046, SPECT\/CT imaging was applied to identify candidate targets for KN046 immunotherapy. [\n                      <jats:sup>18<\/jats:sup>\n                      F]-FDG and [\n                      <jats:sup>68<\/jats:sup>\n                      \u00a0Ga]-NOTA-GZP (granzyme B-specific PET imaging agent) micro-PET\/CT imaging was used to assess the immune response in vivo after [\n                      <jats:sup>131<\/jats:sup>\n                      I]-KN046 treatment. The synergistic treatment effect of [\n                      <jats:sup>131<\/jats:sup>\n                      I]-KN046 was evaluated by exploring the [\n                      <jats:sup>131<\/jats:sup>\n                      I]-based radionuclide-induced release of tumor immunogenicity-related antigens as well as the histology and survival of tumor-bearing mice after treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The constructed [\n                      <jats:sup>131<\/jats:sup>\n                      I]-KN046 exhibited high affinity and specificity for PD-L1\/CTLA-4 immune targets and had excellent in vivo intratumoral retention capability so as to achieve good antitumor efficacy. More importantly, the combination of low-dose [\n                      <jats:sup>131<\/jats:sup>\n                      I] and KN046-enhanced immunosensitivity increased the immunotherapy response rates significantly. Exposure of tumor cells to [\n                      <jats:sup>131<\/jats:sup>\n                      I]-KN046 led to upregulated expression of MHC-I and Fas surface molecules and significant increases in the degree of T-cell activation and counts of tumor-infiltrating immunocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Use of low-dose [\n                      <jats:sup>131<\/jats:sup>\n                      I] combined with a dual-target immunosuppressant could be exploited to identify the subset of treatment responders but also exhibited great potential for enhancing antitumor immune responses.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-022-05986-4","type":"journal-article","created":{"date-parts":[[2022,10,15]],"date-time":"2022-10-15T00:02:44Z","timestamp":1665792164000},"page":"275-286","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Enhanced antitumor immune responses via a new agent [131I]-labeled dual-target immunosuppressant"],"prefix":"10.1007","volume":"50","author":[{"given":"Chunjuan","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiwei","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panli","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bolin","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2544-7522","authenticated-orcid":false,"given":"Shaoli","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,15]]},"reference":[{"key":"5986_CR1","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1200\/JCO.2014.56.2736","volume":"33","author":"D Schadendorf","year":"2015","unstructured":"Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, et al. 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