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dc.creatorÁlvarez, M. (Maite)-
dc.creatorOtano, I. (Itziar)-
dc.creatorMinute, L. (Luna)-
dc.creatorOchoa, M.C. (María Carmen)-
dc.creatorPerez-Ruiz, E. (Elisabeth)-
dc.creatorMelero, I. (Ignacio)-
dc.creatorBerraondo, P. (Pedro)-
dc.date.accessioned2021-10-27T09:21:38Z-
dc.date.available2021-10-27T09:21:38Z-
dc.date.issued2019-
dc.identifier.citationÁlvarez, M. (Maite); Otano, I. (Itziar); Minute, L. (Luna); et al. "Impact of prophylactic TNF blockade in the dual PD-1 and CTLA-4 immunotherapy efficacy and toxicity". Cell Stress. 3 (7), 2019, 236 - 239es_ES
dc.identifier.issn2523-0204-
dc.identifier.urihttps://hdl.handle.net/10171/62286-
dc.description.abstractThe TNF blockade therapy is currently a well-established treatment option for a variety of autoimmune diseases such as rheumatoid arthritis (RA), psoriasis or Crohn's disease, given the proinflammatory role of TNF in the course of these diseases. Importantly, TNF neutralization is also used for the treatment of corticosteroid-refractory immune-related adverse events (irAEs) induced by the combined anti-PD-1 and anti-CTLA-4 immunotherapy. The manifestation of these toxicities is an important limiting factor for the successful implementation of the inhibitory checkpoint blockade therapy (ICB), restraining its anti-tumor efficacy. In our recent study (Perez-Ruiz et al., Nature 569(7756): 428-432.), we analyzed the potential impact of prophylactic TNF neutralization therapy in the anti-PD1/CTLA-4 efficacy. Through several mouse models, we demonstrated that TNF neutralization ameliorated ICB-exacerbated colitis in addition to improving ICB-dependent anti-tumor efficacy. Similar results were obtained after prophylactic TNF blockade in graft vs host xenografted mouse models with human immune cells, which showed a reduction in colitis and hepatitis. Importantly, there was a preservation of the immunotherapeutic control of xenografted tumors after ICB treatment. Moreover, TNF and TNF-dependent gene expression is upregulated in the colon mucosa from patients affected by colitis as a side effect of ipilimumab and nivolumab. Our results, thus, provide evidence of the successful combination of prophylactic TNF neutralization with ICB therapy strategy to ameliorate toxicities, while keeping or even ameliorating anti-tumor efficacy. The prophylactic TNF blockade strategy is clinically feasible since excellent TNF inhibitors have been approved for the treatment of autoimmunity and are used for the immune-related serious adverse events in immunotherapy.es_ES
dc.description.sponsorshipI.M. reports advisory roles with Roche-Genentech, BristolMyers Squibb, CYTOMX, Incyte, MedImmune, Tusk, F-Star,Genmab, Molecular Partners, Alligator, Bioncotech, MSD, Merck-Serono and Bayer, and research funding from Roche, BMS, Alligator, and Bioncotech. P.B. reports advisory roles with Tusk and Moderna, research funding from Sanofi, Moderna and Bavarian Nordic and speaker honoraria from BMS, MSD, Novartis and AstraZeneca.es_ES
dc.description.sponsorshipThis work was supported by the International Immuno- Oncology Network (II-ON) from Bristol Myers Squibb; a Worldwide Cancer Research Grant (15-1146); the Aso- ciación Española Contra el Cancer (AECC) Foundation under grant GCB15152947MELE; the Instituto Carlos III (under grants PI14/01686, PI13/00207 and PI16/00668) co- financed with FEDER funds; and the European Union's Horizon 2020 Program (grant agreement no. 635122 PRO- CROP).-
dc.language.isoenges_ES
dc.publisherShared Science Publishers OGes_ES
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/635122/EU-
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectCTLA-4es_ES
dc.subjectPD-1es_ES
dc.subjectImmunotherapyes_ES
dc.subjectCanceres_ES
dc.subjectTumor necrosis factores_ES
dc.subjectToxicityes_ES
dc.subjectColitises_ES
dc.titleImpact of prophylactic TNF blockade in the dual PD-1 and CTLA-4 immunotherapy efficacy and toxicityes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.description.noteThis is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.es_ES
dc.identifier.doi10.15698/cst2019.07.193-
dadun.citation.endingPage239es_ES
dadun.citation.number7es_ES
dadun.citation.publicationNameCell Stresses_ES
dadun.citation.startingPage236es_ES
dadun.citation.volume3es_ES

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