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Article

Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease

1
Université de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, France
2
Department of nuclear medicine, Université de Nantes, CHU de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, France
3
Centre Hospitalier Départemental de Vendée, F-85925 La Roche-Sur-Yon, France
4
ONIRIS, F-44000 Nantes, France
5
Université de Nantes, IMT Atlantique, CNRS, Subatech, F-44000 Nantes, France
6
Groupement d’Intérêt Public Arronax, F-44800 Saint-Herblain, France
7
ICO-René Gauducheau Cancer Center, F-44800 Saint-Herblain, France
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(9), 2721; https://doi.org/10.3390/cancers12092721
Received: 7 September 2020 / Revised: 17 September 2020 / Accepted: 19 September 2020 / Published: 22 September 2020
(This article belongs to the Special Issue PET/CT in Multiple Myeloma Patients)
Multiple myeloma is a cancer that remains incurable. Among the many therapies under evaluation, antibodies can be used as vehicles to target and deliver toxic radiation to the tumour cells. Our objective was therefore to investigate the potential of targeted alpha therapy, combining an anti-CD138 mAb with astatine-211, to destroy the residual cells responsible for relapse. We have shown in a mouse model that mimics human disease, that destroying multiple myeloma cells is feasible with low toxicity by injecting an anti-CD138 mAb coupled with astatine-211. This approach could eradicate residual cells after initial treatment and thus prevent recurrence.
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 211At-9E7.4 radioimmunoconjugate were tested in two independent experiments: 370 kBq (n = 16), 555 kBq (n = 10), 740 kBq (n = 17) and 1100 kBq (n = 6). An isotype control was also tested at 555 kBq (n = 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. View Full-Text
Keywords: Targeted alpha therapy; astatine-211; multiple myeloma; CD138; minimal residual disease Targeted alpha therapy; astatine-211; multiple myeloma; CD138; minimal residual disease
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MDPI and ACS Style

Gouard, S.; Maurel, C.; Marionneau-Lambot, S.; Dansette, D.; Bailly, C.; Guérard, F.; Chouin, N.; Haddad, F.; Alliot, C.; Gaschet, J.; Eychenne, R.; Kraeber-Bodéré, F.; Chérel, M. Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease. Cancers 2020, 12, 2721. https://doi.org/10.3390/cancers12092721

AMA Style

Gouard S, Maurel C, Marionneau-Lambot S, Dansette D, Bailly C, Guérard F, Chouin N, Haddad F, Alliot C, Gaschet J, Eychenne R, Kraeber-Bodéré F, Chérel M. Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease. Cancers. 2020; 12(9):2721. https://doi.org/10.3390/cancers12092721

Chicago/Turabian Style

Gouard, Sébastien, Catherine Maurel, Séverine Marionneau-Lambot, Delphine Dansette, Clément Bailly, François Guérard, Nicolas Chouin, Ferid Haddad, Cyril Alliot, Joëlle Gaschet, Romain Eychenne, Françoise Kraeber-Bodéré, and Michel Chérel. 2020. "Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease" Cancers 12, no. 9: 2721. https://doi.org/10.3390/cancers12092721

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