Promoção Da Saúde No Contexto Universitário: Interesse E Envolvimento Dos Acadêmicos De Enfermagem

Santos, Floriacy Stabnow; Neto, Marcelino Santos; Santos, Romila Martins de Moura Stabnow; Martins, Suzan Karla Leite; Silva, Victor Gabriel Aquino da; Rodrigues, Vitória Caroline de Lima; Lima, Welison Lucas Rodrigues; Santos, Lívia Fernanda Siqueira; Pereira, Ytallo Juan Alves Silva; Fontoura, Iolanda Graepp; Fontoura, Volmar Morais

doi:10.22533/at.ed.94119130629

Cited by 1 publication

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“…EGFRvIII expression is a tumor-speci c event in breast carcinoma, non-small cell lung carcinoma, and some cases of high-grade glioma and can be considered an ideal antigen for immunotherapy [10]. Among currently approved monoclonal antibodies cetuximab, panitumumab, necitumumab, nimotuzumab, and matuzumab targeting domain III of EGFR, only panitumumab can neutralize both wtEGFR and EGFRvIII leading to p-S6 signaling reduction and superior in vitro and in vivo antitumor activity [11,12]. In this study, we utilized ClyA protein to display a high-a nity anti-EGFR ligand on the surface of OMVs.…”

Section: Introductionmentioning

confidence: 99%

Anti-EGFR Bioengineered Bacterial Outer Membrane Vesicles as Targeted Immunotherapy Agents in Triple-Negative Breast Tumor Murine Model

Adriani

Gargari

Bakherad

2023

Preprint

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Cancer immunotherapy using checkpoint inhibitors is considered a promising approach in various cancers, however, around 55–87% of patients fail to respond to this treatment. Combinatorial therapy through targeted nano-size particles carrying various Toll-like receptor (TLR) agonists to the tumor site can enhance the therapeutic index by activation of intratumoral antigen-presenting cell (APC). Outer membrane vesicles (OMVs) secreted by all gram-negative bacteria present various surface-exposed immune stimulators in their native conformation and Toll-like receptor activating components. In this study, OMVs were engineered to target highly overexpressing EGFR cancer cells in vitro. Affinity-based assays with both EGFR positive and negative cells were performed, and the equilibrium dissociation constant (Kd) of the designed scFv was calculated. Then, we employed the syngeneic model of a triple-negative mouse breast cancer, 4T1, to assess the function of bioengineered OMVs in vivo. Bioengineered OMVs were able to attach to EGFR high-expression cells in vitro. Analyzing the effectiveness of these nanovesicles in a triple-negative breast tumor mice model indicated that the administration route plays an important role in stimulating anti-tumor response. Both intraperitoneal (i.p.) and intratumoral (i.t.) injections of bioengineered OMVs stimulated innate immune response by activating natural killer cells and decreasing the rate of M2 macrophage in the tumor microenvironment. Contrary to the i.p. route with significant tumor size reduction, the in i.t. route only the growth of the tumor was inhibited. Considering both in vitro and in vivo results obtained in this study indicates the potential of OMVs as an effective anti-tumor strategy in future studies.

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Section: Introductionmentioning

confidence: 99%