Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease
Despite therapeutic progress in recent years with the introduction of targeted therapies (daratumumab, elotuzumab), multiple myeloma remains an incurable cancer. The question is therefore to investigate the potential of targeted alpha therapy, combining an anti-CD138 antibody with astatine-211, to d...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/9/2721 |
| _version_ | 1797552953262866432 |
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| author | Sébastien Gouard Catherine Maurel Séverine Marionneau-Lambot Delphine Dansette Clément Bailly François Guérard Nicolas Chouin Ferid Haddad Cyril Alliot Joëlle Gaschet Romain Eychenne Françoise Kraeber-Bodéré Michel Chérel |
| author_facet | Sébastien Gouard Catherine Maurel Séverine Marionneau-Lambot Delphine Dansette Clément Bailly François Guérard Nicolas Chouin Ferid Haddad Cyril Alliot Joëlle Gaschet Romain Eychenne Françoise Kraeber-Bodéré Michel Chérel |
| author_sort | Sébastien Gouard |
| collection | DOAJ |
| description | Despite therapeutic progress in recent years with the introduction of targeted therapies (daratumumab, elotuzumab), multiple myeloma remains an incurable cancer. The question is therefore to investigate the potential of targeted alpha therapy, combining an anti-CD138 antibody with astatine-211, to destroy the residual cells that cause relapses. A preclinical syngeneic mouse model, consisting of IV injection of 1 million of 5T33 cells in a KaLwRij C57/BL6 mouse, was treated 10 days later with an anti-mCD138 antibody, called 9E7.4, radiolabeled with astatine-211. Four activities of the <sup>211</sup>At-9E7.4 radioimmunoconjugate were tested in two independent experiments: 370 kBq (<i>n</i> = 16), 555 kBq (<i>n</i> = 10), 740 kBq (<i>n</i> = 17) and 1100 kBq (<i>n</i> = 6). An isotype control was also tested at 555 kBq (<i>n</i> = 10). Biodistribution, survival rate, hematological parameters, enzymatic hepatic toxicity, histological examination and organ dosimetry were considered. The survival median of untreated mice was 45 days after engraftment. While the activity of 1100 kBq was highly toxic, the activity of 740 kBq offered the best efficacy with 65% of overall survival 150 days after the treatment with no evident sign of toxicity. This work demonstrates the pertinence of treating minimal residual disease of multiple myeloma with an anti-CD138 antibody coupled to astatine-211. |
| first_indexed | 2024-03-10T16:08:28Z |
| format | Article |
| id | doaj.art-2e4d22a2ffbb4a3cb77aaa9418d641c5 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T16:08:28Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2e4d22a2ffbb4a3cb77aaa9418d641c52023-11-20T14:41:16ZengMDPI AGCancers2072-66942020-09-01129272110.3390/cancers12092721Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual DiseaseSébastien Gouard0Catherine Maurel1Séverine Marionneau-Lambot2Delphine Dansette3Clément Bailly4François Guérard5Nicolas Chouin6Ferid Haddad7Cyril Alliot8Joëlle Gaschet9Romain Eychenne10Françoise Kraeber-Bodéré11Michel Chérel12Université de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, FranceUniversité de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, FranceDepartment of nuclear medicine, Université de Nantes, CHU de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, FranceCentre Hospitalier Départemental de Vendée, F-85925 La Roche-Sur-Yon, FranceDepartment of nuclear medicine, Université de Nantes, CHU de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, FranceUniversité de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, FranceUniversité de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, FranceUniversité de Nantes, IMT Atlantique, CNRS, Subatech, F-44000 Nantes, FranceUniversité de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, FranceUniversité de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, FranceUniversité de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, FranceDepartment of nuclear medicine, Université de Nantes, CHU de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, FranceUniversité de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, FranceDespite therapeutic progress in recent years with the introduction of targeted therapies (daratumumab, elotuzumab), multiple myeloma remains an incurable cancer. The question is therefore to investigate the potential of targeted alpha therapy, combining an anti-CD138 antibody with astatine-211, to destroy the residual cells that cause relapses. A preclinical syngeneic mouse model, consisting of IV injection of 1 million of 5T33 cells in a KaLwRij C57/BL6 mouse, was treated 10 days later with an anti-mCD138 antibody, called 9E7.4, radiolabeled with astatine-211. Four activities of the <sup>211</sup>At-9E7.4 radioimmunoconjugate were tested in two independent experiments: 370 kBq (<i>n</i> = 16), 555 kBq (<i>n</i> = 10), 740 kBq (<i>n</i> = 17) and 1100 kBq (<i>n</i> = 6). An isotype control was also tested at 555 kBq (<i>n</i> = 10). Biodistribution, survival rate, hematological parameters, enzymatic hepatic toxicity, histological examination and organ dosimetry were considered. The survival median of untreated mice was 45 days after engraftment. While the activity of 1100 kBq was highly toxic, the activity of 740 kBq offered the best efficacy with 65% of overall survival 150 days after the treatment with no evident sign of toxicity. This work demonstrates the pertinence of treating minimal residual disease of multiple myeloma with an anti-CD138 antibody coupled to astatine-211.https://www.mdpi.com/2072-6694/12/9/2721Targeted alpha therapyastatine-211multiple myelomaCD138minimal residual disease |
| spellingShingle | Sébastien Gouard Catherine Maurel Séverine Marionneau-Lambot Delphine Dansette Clément Bailly François Guérard Nicolas Chouin Ferid Haddad Cyril Alliot Joëlle Gaschet Romain Eychenne Françoise Kraeber-Bodéré Michel Chérel Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease Cancers Targeted alpha therapy astatine-211 multiple myeloma CD138 minimal residual disease |
| title | Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease |
| title_full | Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease |
| title_fullStr | Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease |
| title_full_unstemmed | Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease |
| title_short | Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease |
| title_sort | targeted alpha therapy combining astatine 211 and anti cd138 antibody in a preclinical syngeneic mouse model of multiple myeloma minimal residual disease |
| topic | Targeted alpha therapy astatine-211 multiple myeloma CD138 minimal residual disease |
| url | https://www.mdpi.com/2072-6694/12/9/2721 |
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