Radioimmunotherapy involves the selective targeting of therapeutic radionuclides to cancer-associated cell surface antigens using monoclonal antibodies. Radioimmunotherapy has been successful in treating hematologic cancers, such as non-Hodgkin’s Lymphoma. However, treatment of solid tumors by radioimmunotherapy remains a challenge, driven in part by a lack of high affinity antibodies against highly tumor-selective surface antigens. Herein, we characterize novel anti-B7-H3 immuno-conjugates for PET imaging and RIT of solid tumors in preclinical models.
Human B7-H3 (CD276) protein is highly expressed on solid tumor cell surfaces and endovascular surfaces in a wide variety of cancers (colon, breast, pancreatic, prostate, head and neck, glioblastoma, ovarian, and non-squamous cell lung cancer), and is low or absent in normal tissues, an ideal RIT target. First, we developed in-house a high affinity (picomolar) dual species (human, mouse) anti-B7-H3 antibody (MIL33B), validated through biolayer interferometry and ELISA. AF594-labeled MIL33B showed membrane-associated staining of tumor cells natively expressing or induced to overexpress B7-H3, displacement by unlabeled MIL33B, and no staining in knockout cell lines and isotype control, confirming specificity. MIL33B labeled with 89Zr (89Zr-DFO-MIL33B) for PET/CT imaging demonstrated high retention in multiple syngeneic tumor models transfected with human B7-H3 compared to vector controls or tumors imaged with isotype control antibody (89Zr-DFO-IgG2a) and in immunodeficient tumor models with high B7-H3 tumor expression compared to B7-H3 KO tumors.
Next, a single intravenous administration of MIL33B labeled with Yttrium-90 (90Y-DOTA-MIL33B; 100 mCi), a therapeutic beta-emitter, induced complete tumor regression and long-term survival of greater than 50% of mice harboring established syngeneic subcutaneous CT26 tumors, a radio-resistant colorectal cell type transfected with human B7-H3 (CT26 hB7-H3) compared to with tumors transfected with vector control (CT26 vector). Mice whose tumors regressed in response to 90Y-DOTA-MIL33B treatment developed immunologic memory and in vivo depletion assays demonstrated that CD8b+ cells were necessary to confer the therapeutic effects of 90Y-DOTA-MIL33B. These results point to the promise of 90Y-DOTA-MIL33B radioimmunotherapy as a treatment for solid tumors and as a potential immune modulator.
","abstract_html":"<p>Radioimmunotherapy involves the selective targeting of therapeutic radionuclides to cancer-associated cell surface antigens using monoclonal antibodies. Radioimmunotherapy has been successful in treating hematologic cancers, such as non-Hodgkin’s Lymphoma. However, treatment of solid tumors by radioimmunotherapy remains a challenge, driven in part by a lack of high affinity antibodies against highly tumor-selective surface antigens. Herein, we characterize novel<sup> </sup>anti-B7-H3 immuno-conjugates for PET imaging and RIT of solid tumors in preclinical models.</p> <p>Human B7-H3 (CD276) protein is highly expressed on solid tumor cell surfaces and endovascular surfaces in a wide variety of cancers (colon, breast, pancreatic, prostate, head and neck, glioblastoma, ovarian, and non-squamous cell lung cancer), and is low or absent in normal tissues, an ideal RIT target. First, we developed in-house a high affinity (picomolar) dual species (human, mouse) anti-B7-H3 antibody (MIL33B), validated through biolayer interferometry and ELISA. AF594-labeled MIL33B showed membrane-associated staining of tumor cells natively expressing or induced to overexpress B7-H3, displacement by unlabeled MIL33B, and no staining in knockout cell lines and isotype control, confirming specificity. MIL33B labeled with <sup>89</sup>Zr (<sup>89</sup>Zr-DFO-MIL33B) for PET/CT imaging demonstrated high retention in multiple syngeneic tumor models transfected with human B7-H3 compared to vector controls or tumors imaged with isotype control antibody (<sup>89</sup>Zr-DFO-IgG2a) and in immunodeficient tumor models with high B7-H3 tumor expression compared to B7-H3 KO tumors.</p> <p>Next, a single intravenous administration of MIL33B labeled with Yttrium-90 (<sup>90</sup>Y-DOTA-MIL33B; 100 mCi), a therapeutic beta-emitter, induced complete tumor regression and long-term survival of greater than 50% of mice harboring established syngeneic subcutaneous CT26 tumors, a radio-resistant colorectal cell type transfected with human B7-H3 (CT26 hB7-H3) compared to with tumors transfected with vector control (CT26 vector). Mice whose tumors regressed in response to <sup>90</sup>Y-DOTA-MIL33B treatment developed immunologic memory and <em>in vivo </em>depletion assays demonstrated that CD8b+ cells were necessary to confer the therapeutic effects of <sup>90</sup>Y-DOTA-MIL33B. These results point to the promise of <sup>90</sup>Y-DOTA-MIL33B radioimmunotherapy as a treatment for solid tumors and as a potential immune modulator.</p>","abstract_has_math":false,"creators":["Glazer, Sarah","0000-0001-9384-1287
"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["David Piwnica-Worms, M.D., Ph.D.","Scott Evans, M.D.","Jeffrey Molldrem, M.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-05-01T07:00:00Z","date_published":"2022-05-01T07:00:00Z","updated_at":"2026-07-24T05:50:02Z","subjects":["solid tumors","radioimmunotherapy","theranostics","PET","B7-H3","antibody","beta-emitters","Cancer Biology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1174","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["David Piwnica-Worms, M.D., Ph.D.","Scott Evans, M.D.","Jeffrey Molldrem, M.D."]},{"key":"dc:creator","label":"Author","values":["Glazer, Sarah","0000-0001-9384-1287
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Human B7-H3 (CD276) protein is highly expressed on solid tumor cell surfaces and endovascular surfaces in a wide variety of cancers (colon, breast, pancreatic, prostate, head and neck, glioblastoma, ovarian, and non-squamous cell lung cancer), and is low or absent in normal tissues, an ideal RIT target. First, we developed in-house a high affinity (picomolar) dual species (human, mouse) anti-B7-H3 antibody (MIL33B), validated through biolayer interferometry and ELISA. AF594-labeled MIL33B showed membrane-associated staining of tumor cells natively expressing or induced to overexpress B7-H3, displacement by unlabeled MIL33B, and no staining in knockout cell lines and isotype control, confirming specificity. MIL33B labeled with 89Zr (89Zr-DFO-MIL33B) for PET/CT imaging demonstrated high retention in multiple syngeneic tumor models transfected with human B7-H3 compared to vector controls or tumors imaged with isotype control antibody (89Zr-DFO-IgG2a) and in immunodeficient tumor models with high B7-H3 tumor expression compared to B7-H3 KO tumors.
Next, a single intravenous administration of MIL33B labeled with Yttrium-90 (90Y-DOTA-MIL33B; 100 mCi), a therapeutic beta-emitter, induced complete tumor regression and long-term survival of greater than 50% of mice harboring established syngeneic subcutaneous CT26 tumors, a radio-resistant colorectal cell type transfected with human B7-H3 (CT26 hB7-H3) compared to with tumors transfected with vector control (CT26 vector). Mice whose tumors regressed in response to 90Y-DOTA-MIL33B treatment developed immunologic memory and in vivo depletion assays demonstrated that CD8b+ cells were necessary to confer the therapeutic effects of 90Y-DOTA-MIL33B. These results point to the promise of 90Y-DOTA-MIL33B radioimmunotherapy as a treatment for solid tumors and as a potential immune modulator.
"]},{"key":"dc:title","label":"Title","values":["Development and Characterization of B7-H3-Targeted Radioimmunotherapies For The Treatment of Solid Tumors"]}]}],"canonical_facts":{"dc:contributor":["David Piwnica-Worms, M.D., Ph.D.","Scott Evans, M.D.","Jeffrey Molldrem, M.D."],"dc:creator":["Glazer, Sarah","0000-0001-9384-1287
"],"dc:date.available":["2023-04-27T07:00:00Z"],"dc:description.abstract":["Radioimmunotherapy involves the selective targeting of therapeutic radionuclides to cancer-associated cell surface antigens using monoclonal antibodies. Radioimmunotherapy has been successful in treating hematologic cancers, such as non-Hodgkin’s Lymphoma. However, treatment of solid tumors by radioimmunotherapy remains a challenge, driven in part by a lack of high affinity antibodies against highly tumor-selective surface antigens. Herein, we characterize novel anti-B7-H3 immuno-conjugates for PET imaging and RIT of solid tumors in preclinical models.
Human B7-H3 (CD276) protein is highly expressed on solid tumor cell surfaces and endovascular surfaces in a wide variety of cancers (colon, breast, pancreatic, prostate, head and neck, glioblastoma, ovarian, and non-squamous cell lung cancer), and is low or absent in normal tissues, an ideal RIT target. First, we developed in-house a high affinity (picomolar) dual species (human, mouse) anti-B7-H3 antibody (MIL33B), validated through biolayer interferometry and ELISA. AF594-labeled MIL33B showed membrane-associated staining of tumor cells natively expressing or induced to overexpress B7-H3, displacement by unlabeled MIL33B, and no staining in knockout cell lines and isotype control, confirming specificity. MIL33B labeled with 89Zr (89Zr-DFO-MIL33B) for PET/CT imaging demonstrated high retention in multiple syngeneic tumor models transfected with human B7-H3 compared to vector controls or tumors imaged with isotype control antibody (89Zr-DFO-IgG2a) and in immunodeficient tumor models with high B7-H3 tumor expression compared to B7-H3 KO tumors.
Next, a single intravenous administration of MIL33B labeled with Yttrium-90 (90Y-DOTA-MIL33B; 100 mCi), a therapeutic beta-emitter, induced complete tumor regression and long-term survival of greater than 50% of mice harboring established syngeneic subcutaneous CT26 tumors, a radio-resistant colorectal cell type transfected with human B7-H3 (CT26 hB7-H3) compared to with tumors transfected with vector control (CT26 vector). Mice whose tumors regressed in response to 90Y-DOTA-MIL33B treatment developed immunologic memory and in vivo depletion assays demonstrated that CD8b+ cells were necessary to confer the therapeutic effects of 90Y-DOTA-MIL33B. These results point to the promise of 90Y-DOTA-MIL33B radioimmunotherapy as a treatment for solid tumors and as a potential immune modulator.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1174"],"dc:subject":["solid tumors","radioimmunotherapy","theranostics","PET","B7-H3","antibody","beta-emitters","Cancer Biology"],"dc:title":["Development and Characterization of B7-H3-Targeted Radioimmunotherapies For The Treatment of Solid Tumors"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:50:02Z"}