Case study #2: Disialoganglioside GD2 as a target for radiopharmaceutical therapy Book Section
| Authors: | Cheung, N. K. V.; Kramer, K.; Modak, S.; Kushner, B. H.; Ahmed, M.; Santich, B.; Cheal, S.; Larson, S. |
| Editors: | Bodei, L.; Lewis, J. S.; Zeglis, B. M. |
| Article/Chapter Title: | Case study #2: Disialoganglioside GD2 as a target for radiopharmaceutical therapy |
| Abstract: | Disialoganglioside GD2 is found in stem cells, some neurons and nerve fibers, and the basal layer of the skin and is overexpressed in solid tumors, including neuroblastoma, osteosarcoma, soft tissue sarcomas, and others. Dinutuximab (chimeric 14.18) and naxitamab (humanized 3F8 or hu3F8) are Food and Drug Administration (FDA)-approved monoclonal antibodies (mAb) that are specific for the penta-oligosaccharide epitope in GD2. Immuno-oncology, radioimmunodiagnosis (RID), and radioimmunotherapy (RIT) investigations with 3F8, a murine Immunoglobulin G3 (IgG3), formed the basis for the clinical development of hu3F8. The exceptional tumor selectivity of murine 3F8 in preclinical models quickly translated into clinical studies with 131I- and 124I-labeled 3F8 in the early 1990s, building a strong clinical rationale for RIT with the same platform. Yet patient survival did not improve at myeloablative doses of intravenous 131I-3F8 that required stem cell rescue. To achieve a curative therapeutic index (TI, area under the curvetumor (AUCtumor) vs. AUCnormal organs), compartmental intraommaya 131I-3F8 was developed with modest success in patients with leptomeningeal indications. Most recently, pretargeted radioimmunotherapy (PRIT) using a radiolabeled, DOTA (1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based hapten has shown promise by combining the tumor targeting properties of an immunoglobulin with the rapid pharmacokinetic profile of a small molecule. This approach is non-immunogenic, does not produce neuropathic side effects, is modular, and can achieve high therapeutic indices for critical organs such as marrow, kidney, liver, and gut. This novel technology should help RIT scale the hurdle for successful clinical translation. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023. |
| Keywords: | <sup>131</sup>i; radioimmunotherapy; gd2; pretargeted radioimmunotherapy; hu3f8; disialo-ganglioside gd2 |
| Book Title: | Radiopharmaceutical Therapy |
| ISBN: | 978-3-031-39004-3 |
| Publisher: | Springer |
| Publication Place: | Cham, Switzerland |
| Date Published: | 2023-01-01 |
| Start Page: | 225 |
| End Page: | 252 |
| Language: | English |
| DOI: | 10.1007/978-3-031-39005-0_11 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Book chapter: 11 -- Source: Scopus |
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