Full metadata record
DC Field | Value | Language |
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dc.creator | Ochoa, M.C. (María Carmen) | - |
dc.creator | Minute, L. (Luna) | - |
dc.creator | Lopez, A. (Ascensión) | - |
dc.creator | Perez-Ruiz, E. (Elisabeth) | - |
dc.creator | Gomar, C. (Celia) | - |
dc.creator | Vasquez, M. (Marcos) | - |
dc.creator | Inoges, S. (Susana) | - |
dc.creator | Etxeberria, I. (Iñaki) | - |
dc.creator | Rodriguez, I. (Inmaculada) | - |
dc.creator | Garasa, S. (Saray) | - |
dc.creator | Mayer, J.P. (Jan Peter) | - |
dc.creator | Wirtz, P. (Peter) | - |
dc.creator | Melero, I. (Ignacio) | - |
dc.creator | Berraondo, P. (Pedro) | - |
dc.date.accessioned | 2022-10-19T07:51:22Z | - |
dc.date.available | 2022-10-19T07:51:22Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Ochoa, M.C. (María Carmen); Minute, L. (Luna); Lopez, A. (Ascensión); et al. "Enhancement of antibody-dependent cellular cytotoxicity of cetuximab by a chimeric protein encompassing interleukin-15". Oncoinmunology. 7 (2), 2018, e1393597 | es_ES |
dc.identifier.issn | 2162-402X | - |
dc.identifier.uri | https://hdl.handle.net/10171/64487 | - |
dc.description.abstract | Enhancement of antibody-dependent cellular cytotoxicity (ADCC) may potentiate the antitumor efficacy of tumor-targeted monoclonal antibodies. Increasing the numbers and antitumor activity of NK cells is a promising strategy to maximize the ADCC of standard-of-care tumor-targeted antibodies. For this purpose, we have preclinically tested a recombinant chimeric protein encompassing the sushi domain of the IL15Rα, IL-15, and apolipoprotein A-I (Sushi-IL15-Apo) as produced in CHO cells. The size-exclusion purified monomeric fraction of this chimeric protein was stable and retained the IL-15 and the sushi domain bioactivity as measured by CTLL-2 and Mo-7e cell proliferation and STAT5 phosphorylation in freshly isolated human NK and CD8+ T cells. On cell cultures, Sushi-IL15-Apo increases NK cell proliferation and survival as well as spontaneous and antibody-mediated cytotoxicity. Scavenger receptor class B type I (SR-B1) is the receptor for ApoA-I and is expressed on the surface of tumor cells. SR-B1 can adsorb the chimeric protein on tumor cells and can transpresent IL-15 to NK and CD8+ T cells. A transient NK-humanized murine model was developed to test the increase of ADCC attained by the chimeric protein in vivo. The EGFR+ human colon cancer cell line HT-29 was intraperitoneally inoculated in immune-deficient Rag2-/-γc-/- mice that were reconstituted with freshly isolated PBMCs and treated with the anti-EGFR mAb cetuximab. The combination of the Sushi-IL15-Apo protein and cetuximab reduced the number of remaining tumor cells in the peritoneal cavity and delayed tumor engraftment in the peritoneum. Furthermore, Sushi-IL15-Apo increased the anti-tumor effect of a murine anti-EGFR mAb in Rag1-/- mice bearing subcutaneous MC38 colon cancer transfected to express EGFR. Thus, Sushi-IL15-Apo is a potent tool to increase the number and the activation of NK cells to promote the ADCC activity of antibodies targeting tumor antigens. | es_ES |
dc.description.sponsorship | This work was supported by Worldwide Cancer Research Grant under Grant 15–1146, Asociacion Espanola Contra el Cancer (AECC) Founda- ~ tion under Grant GCB15152947MELE, Red Tematica de Investigacion Cooperativa en Cancer under Grants RD12/0036/0040 and RD12/0036/ 0062, Fondo de Investigaci on Sanitaria-Fondo Europeo de Desarrollo Regional (FEDER) under Grants PI14/01686, PI13/00207, PI16/00668, and H2020 PROCROP project under Grant 635122. P.B. is supported by Miguel Servet II (CPII15/00004) contract from Instituto de Salud Carlos III. EP-R is supported by the Carmen Lavigne training program of Asociacion Espanola contra el Cancer and by Consejeria de Salud de la ~ Junta de Andaluc ıa. We thank Dr. Pablo Umana for providing EGFR ~ CMC38 cells. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Taylor & Francis | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.subject | Interleukin 15 | es_ES |
dc.subject | Apolipoprotein A-I | es_ES |
dc.subject | Scavenger receptor class B type I | es_ES |
dc.subject | Antibody-dependent cellular cytotoxicity | es_ES |
dc.subject | NK cell | es_ES |
dc.subject | Cetuximab | es_ES |
dc.title | Enhancement of antibody-dependent cellular cytotoxicity of cetuximab by a chimeric protein encompassing interleukin-15 | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.identifier.doi | 10.1080/2162402X.2017.1393597 | - |
dadun.citation.number | 2 | es_ES |
dadun.citation.publicationName | Oncoinmunology | es_ES |
dadun.citation.startingPage | e1393597 | es_ES |
dadun.citation.volume | 7 | es_ES |
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