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

Rodríguez López, José Neptuno; Sánchez del Campo, Luis; Martí Díaz, Román; Montenegro, María F; Hernández Caselles, Trinidad; Piñero Madrona, Antonio; Cabezas Herrera, Juan

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

dc.contributor.author	Rodríguez López, José Neptuno
dc.contributor.author	Sánchez del Campo, Luis
dc.contributor.author	Martí Díaz, Román
dc.contributor.author	Montenegro, María F
dc.contributor.author	Hernández Caselles, Trinidad
dc.contributor.author	Piñero Madrona, Antonio
dc.contributor.author	Cabezas Herrera, Juan
dc.contributor.department	Bioquímica y Biología Molecuar A
dc.contributor.department	IMIB Pascual Parrilla
dc.date.accessioned	2025-03-12T11:18:25Z
dc.date.available	2025-03-12T11:18:25Z
dc.date.created	2025
dc.description.abstract	Background: 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 cell-based 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.identifier.uri	http://hdl.handle.net/10201/151680
dc.language	eng	es
dc.relation	Ministerio de Ciencia, Innovación y Universidades (MICIU) [Projects PID2023-149281OB-I00 & CPP2023-010510 (MICIU/AEI/10.13039/ 501100011033 & FEDER, UE). Fundación Séneca – Agencia de Ciencia y Tecnología de la Región de Murcia [FSRM/10.13039/100007801(22544/PI/24). Spain]. Fundación Séneca. Región de Murcia (Spain) (21407/FPI/20).	es
dc.relation.isrequiredby	http://hdl.handle.net/10201/156952
dc.rights	info:eu-repo/semantics/openAccess	es
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/	*
dc.subject	Breast cancer	es
dc.subject	Whole tumor cell-based vaccines	es
dc.subject	CD47	es
dc.subject	Lonizing radiation	es
dc.subject	Anti-tumor immunity	es
dc.title	Ex vivo engineering of phagocytic signals in breast cancer cells for a whole tumor cell-based vaccine	es
dc.type	info:eu-repo/semantics/dataset	es
dspace.entity.type	Publication	es

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