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Here, the effect of the anti-CD37 antibody-radionuclide conjugate lutetium-177 (<jats:sup>177<\/jats:sup>Lu)-lilotomab (Betalutin<jats:sup>\u00ae<\/jats:sup>) was investigated in preclinical models of NHL. In SCID mice bearing DOHH2 (transformed follicular lymphoma, FL) cell xenografts,<jats:sup>177<\/jats:sup>Lu-lilotomab significantly delayed tumor growth, even at low activity (100\u2009MBq\/kg). In athymic mice bearing OCI-Ly8 (diffuse large B-cell lymphoma, DLBCL) or Ramos (Burkitt\u2019s lymphoma) cell xenografts,<jats:sup>177<\/jats:sup>Lu-lilotomab activity had to be increased to 500\u2009MBq\/kg to show a significant tumor growth delay. Clonogenic and proliferation assays showed that DOHH2 cells were highly sensitive to<jats:sup>177<\/jats:sup>Lu-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<jats:sup>177<\/jats:sup>Lu-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,<jats:sup>177<\/jats:sup>Lu-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<jats:sup>177<\/jats:sup>Lu-lilotomab is particularly efficient in treating tumors with reduced inhibitory CDK1 phosphorylation, such as transformed FL.<\/jats:p>","DOI":"10.1038\/s41375-019-0677-4","type":"journal-article","created":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T11:04:00Z","timestamp":1576235040000},"page":"1315-1328","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The therapeutic effectiveness of 177Lu-lilotomab in B-cell non-Hodgkin lymphoma involves modulation of G2\/M cell cycle arrest"],"prefix":"10.1038","volume":"34","author":[{"given":"Alexandre","family":"Pichard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Marcatili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihad","family":"Karam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Constanzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riad","family":"Ladjohounlou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Courteau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Jarlier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Bonnefoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Patzke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilde","family":"Stenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Coopman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Cartron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Navarro-Teulon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ada","family":"Repetto-Llamazares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Heyerdahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jostein","family":"Dahle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Bardi\u00e8s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Pouget","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,13]]},"reference":[{"key":"677_CR1","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1182\/blood.V83.2.435.435","volume":"83","author":"ME Reff","year":"1994","unstructured":"Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, et al. 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