A recombinant adenovirus vector containing the synNotch receptor gene for the treatment of triple-negative breast cancer

Ruhan, A; Kunimura, Naoto; Tominaga, Shoko; Hirata, Erika; Nishioka, Shunya; Uesugi, Misato; Yamazaki, Rion; Ueki, Hideto; Kitagawa, Koichi; Fujisawa, Masato; Shirakawa, Toshiro

doi:10.3389/fonc.2023.1147668

Cited by 1 publication

(1 citation statement)

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“…Likewise, the intranasal administration of Advs allows high transduction efficiency in the lung, thus it has been proposed to treat lung metastases [ 78 ]. Recently, an Adv encoding for a hypoxia-inducible factor (HIF)-3α4 and CD44 decoy protein system that is activated by Notch ligands has demonstrated efficacy in murine models of human TNBC subtypes [ 79 ]. Here, we observed robust transduction efficiency of Ad.dTomato and Ad.P60 in murine BRCA cells both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Targeting FOXP3 Tumor-Intrinsic Effects Using Adenoviral Vectors in Experimental Breast Cancer

Nicola Candia,

Garcia Fallit,

Peña Agudelo

et al. 2023

Viruses

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The regulatory T cell master transcription factor, Forkhead box P3 (Foxp3), has been detected in cancer cells; however, its role in breast tumor pathogenesis remains controversial. Here we assessed Foxp3 tumor intrinsic effects in experimental breast cancer using a Foxp3 binder peptide (P60) that impairs Foxp3 nuclear translocation. Cisplatin upregulated Foxp3 expression in HER2+ and triple-negative breast cancer (TNBC) cells. Foxp3 inhibition with P60 enhanced chemosensitivity and reduced cell survival and migration in human and murine breast tumor cells. We also developed an adenoviral vector encoding P60 (Ad.P60) that efficiently transduced breast tumor cells, reduced cell viability and migration, and improved the cytotoxic response to cisplatin. Conditioned medium from transduced breast tumor cells contained lower levels of IL-10 and improved the activation of splenic lymphocytes. Intratumoral administration of Ad.P60 in breast-tumor-bearing mice significantly reduced tumor infiltration of Tregs, delayed tumor growth, and inhibited the development of spontaneous lung metastases. Our results suggest that Foxp3 exerts protumoral intrinsic effects in breast cancer cells and that gene-therapy-mediated blockade of Foxp3 could constitute a therapeutic strategy to improve the response of these tumors to standard treatment.

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Section: Discussionmentioning

confidence: 99%