| Added by | Nathalie Bonnefoy |
|---|---|
| Group name | EquipeNB |
| Item Type | Journal Article |
| Title | The therapeutic effectiveness of 177Lu-lilotomab in B-cell non-Hodgkin lymphoma involves modulation of G2/M cell cycle arrest |
| Creator | Pichard et al. |
| Author | Alexandre Pichard |
| Author | Sara Marcatili |
| Author | Jihad Karam |
| Author | Julie Constanzo |
| Author | Riad Ladjohounlou |
| Author | Alan Courteau |
| Author | Marta Jarlier |
| Author | Nathalie Bonnefoy |
| Author | Sebastian Patzke |
| Author | Vilde Stenberg |
| Author | Peter Coopman |
| Author | Guillaume Cartron |
| Author | Isabelle Navarro-Teulon |
| Author | Ada Repetto-Llamazares |
| Author | Helen Heyerdahl |
| Author | Jostein Dahle |
| Author | Manuel Bardiès |
| Author | Jean-Pierre Pouget |
| Abstract | Some patients with B-cell non-Hodkin lymphoma Lymphoma (NHL) become refractory to rituximab (anti-CD20 antibody) therapy associated with chemotherapy. Here, the effect of the anti-CD37 antibody-radionuclide conjugate lutetium-177 (177Lu)-lilotomab (Betalutin®) was investigated in preclinical models of NHL. In SCID mice bearing DOHH2 (transformed follicular lymphoma, FL) cell xenografts, 177Lu-lilotomab significantly delayed tumor growth, even at low activity (100?MBq/kg). In athymic mice bearing OCI-Ly8 (diffuse large B-cell lymphoma, DLBCL) or Ramos (Burkitt's lymphoma) cell xenografts, 177Lu-lilotomab activity had to be increased to 500?MBq/kg to show a significant tumor growth delay. Clonogenic and proliferation assays showed that DOHH2 cells were highly sensitive to 177Lu-lilotomab, while Ramos cells were the least sensitive, and U2932 (DLBCL), OCI-Ly8, and Rec-1 (mantle cell lymphoma) cells displayed intermediate sensitivity. The strong 177Lu-lilotomab cytotoxicity observed in DOHH2 cells correlated with reduced G2/M cell cycle arrest, lower WEE-1- and MYT-1-mediated phosphorylation of cyclin-dependent kinase-1 (CDK1), and higher apoptosis. In agreement, 177Lu-lilotomab efficacy in vitro, in vivo, and in patient samples was increased when combined with G2/M cell cycle arrest inhibitors (MK-1775 and PD-166285). These results indicate that 177Lu-lilotomab is particularly efficient in treating tumors with reduced inhibitory CDK1 phosphorylation, such as transformed FL. |
| Publication | Leukemia |
| Volume | 34 |
| Issue | 5 |
| Pages | 1315-1328 |
| Date | May 2020 |
| Journal Abbr | Leukemia |
| Language | eng |
| DOI | 10.1038/s41375-019-0677-4 |
| ISSN | 1476-5551 |
| Library Catalog | PubMed |
| Extra | PMID: 31836849 PMCID: PMC7192854 |
| Tags | Antibodies, Radiothérapie |
| Date Added | 2020/07/29 - 15:07:14 |
| Date Modified | 2020/07/29 - 15:17:38 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
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