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dc.creatorOchoa, M.C. (María Carmen)-
dc.creatorMinute, L. (Luna)-
dc.creatorLopez, A. (Ascensión)-
dc.creatorPerez-Ruiz, E. (Elisabeth)-
dc.creatorGomar, C. (Celia)-
dc.creatorVasquez, M. (Marcos)-
dc.creatorInoges, S. (Susana)-
dc.creatorEtxeberria, I. (Iñaki)-
dc.creatorRodriguez, I. (Inmaculada)-
dc.creatorGarasa, S. (Saray)-
dc.creatorMayer, J.P. (Jan Peter)-
dc.creatorWirtz, P. (Peter)-
dc.creatorMelero, I. (Ignacio)-
dc.creatorBerraondo, P. (Pedro)-
dc.date.accessioned2022-10-19T07:51:22Z-
dc.date.available2022-10-19T07:51:22Z-
dc.date.issued2018-
dc.identifier.citationOchoa, 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, e1393597es_ES
dc.identifier.issn2162-402X-
dc.identifier.urihttps://hdl.handle.net/10171/64487-
dc.description.abstractEnhancement 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.sponsorshipThis 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.isoenges_ES
dc.publisherTaylor & Francises_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectInterleukin 15es_ES
dc.subjectApolipoprotein A-Ies_ES
dc.subjectScavenger receptor class B type Ies_ES
dc.subjectAntibody-dependent cellular cytotoxicityes_ES
dc.subjectNK celles_ES
dc.subjectCetuximabes_ES
dc.titleEnhancement of antibody-dependent cellular cytotoxicity of cetuximab by a chimeric protein encompassing interleukin-15es_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.identifier.doi10.1080/2162402X.2017.1393597-
dadun.citation.number2es_ES
dadun.citation.publicationNameOncoinmunologyes_ES
dadun.citation.startingPagee1393597es_ES
dadun.citation.volume7es_ES

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