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Ex vivo engineering of phagocytic signals in breast cancer cells for a whole tumor cell-based vaccine

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dc.contributor.authorMartí Díaz, Román
dc.contributor.authorPiñero Madrona, Antonio
dc.contributor.authorCabezas Herrera, Juan
dc.contributor.authorMontenegro Arce, María Fernanda
dc.contributor.authorHernández Caselles, Trinidad
dc.contributor.authorRodríguez López, José Neptuno
dc.contributor.authorSánchez del Campo Ferrer, Luis
dc.contributor.departmentBioquímica y Biología Molecular Aes
dc.date.accessioned2025-07-04T11:35:23Z
dc.date.available2025-07-04T11:35:23Z
dc.date.issued2025-07-01
dc.description© 2025 The authors.____ This document is the published version of a published work that appeared in final form in BMC Cancer This document is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0 To access the final edited and published work see: https://doi.org/10.1186/s12885-025-144321
dc.description.abstractBackground Today, cell therapies are constantly evolving and providing new options for cancer patients. These therapies are mostly based on the inoculation of immune cells extracted from a person’s own tumor; however, some studies using whole tumor cell-based vaccines are approaching the level of maturity required for clinical use. Although these latest therapies will have to be developed further and adapted to overcome many ethical barriers, there is no doubt that therapeutic cancer vaccines are the next frontier of immunotherapy. Methods Ionizing radiation and CD47 knockout via CRISPR-Cas9 genome editing were used to optimize the macrophage-mediated phagocytosis of breast cancer cells. These cells were subsequently used in several mouse models to determine their potential as novel whole-cell-based vaccines to drive antitumor immunity. To improve the recognition of tumor cells by activated immune cells, this cellular therapy was combined with anti-PD-1 antibody treatments. Results Here, we showed that irradiation of 4T1 breast cancer cells increases their immunogenicity and, when injected into the blood of immunocompetent mice, elicits a complete antitumor immune response mediated, in part, by the adaptive immune system. Next, to improve the macrophage-mediated phagocytosis of breast cancer cells, we knocked out CD47 in 4T1 cells. When injected in the bloodstream, irradiated CD47 knockout cells activated both the adaptive and the innate immune systems. Therefore, we used these ex vivo engineered cells as a whole tumor cellbased vaccine to treat breast tumors in immunocompetent mice. A better response was obtained when these cells were combined with an anti-PD-1 antibody. Conclusion These results suggest that tumor cells obtained from surgical samples of a breast cancer patient could be engineered ex vivo and used as a novel cell therapy to drive antitumor immunity.es
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dc.format.extent15es
dc.identifier.citationBMC Cancer
dc.identifier.doi10.1186/s12885-025-14432-1
dc.identifier.issn1471-2407
dc.identifier.urihttp://hdl.handle.net/10201/156952
dc.languageenges
dc.relationThis work was supported by grants from the Ministerio de Ciencia, Innovación y Universidades (MICIU) [Projects PID2023-149281OB-I00 & CPP2023-010510 (MICIU/AEI/10.13039/ 501100011033 & FEDER, UE), and Fundación Séneca– Agencia de Ciencia y Tecnología de la Región de Murcia [FSRM/https://doi.org/10.13039/100007801(22544/PI/24). Spain]. R.M.D. has a fellowship from Fundación Séneca. Región de Murcia (Spain) (21407/FPI/20).es
dc.relation.requireshttp://hdl.handle.net/10201/151680es
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectBreast canceres
dc.subjectWhole tumor cell-based vaccineses
dc.subjectCD47es
dc.subjectIonizing radiationes
dc.subjectAnti-tumor immunityes
dc.titleEx vivo engineering of phagocytic signals in breast cancer cells for a whole tumor cell-based vaccinees
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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