Browsing by Subject "Ionizing radiation"

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    Open Access
    Antiangiogenic and radiotherapy for cancer treatment
    (Murcia : F. Hernández, 2006) Kobayashi, H.; Lin, P.C.
    Tumor growth and progression depends on tumor angiogenesis, the growth of tumor blood vessels, therefore, targeting tumor angiogenesis is a very promising approach for controlling tumor growth and/or causing regression. Tumor blood vessels have been recognized as a critical component of radiation response to the point of being independent of tumor oxygenation during radiation. An anti-angiogenic approach has been considered less likely to develop drug resistance. But recent findings suggest that anti-angiogenesis causes hypoxia that selects tumor cells (due to genetic instability) that are less dependent on blood supply and leads to drug resistance. The approach of combination of anti-angiogenesis with ionizing radiation by targeting both endothelial and tumor cells should minimize this possibility. The combination may produce a synergistic anti-tumor effect.
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    Open Access
    Ex vivo engineering of phagocytic signals in breast cancer cells for a whole tumor cell-based vaccine
    (2025-07-01) Martí Díaz, Román; Piñero Madrona, Antonio; Cabezas Herrera, Juan; Montenegro Arce, María Fernanda; Hernández Caselles, Trinidad; Rodríguez López, José Neptuno; Sánchez del Campo Ferrer, Luis; Bioquímica y Biología Molecular A
    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 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.