BRYAN ERIC STRAUSS
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- Interferons: key modulators of the immune system in cancer(2023) YUSUF, Nabiha; ALLIE, S. Rameeza; STRAUSS, Bryan E.
- Stable expression of shRNA for the control of recombinant adenovirus replication(2023) LANA, M. V. G.; ANTUNES, F.; TESSAROLLO, N. G.; STRAUSS, B. E.Preventing the replication of adenovirus could have practical uses, such as controlling infection with wild-type virus or in applications involving recombinant vectors. Mainly transient methods have been used to inhibit adenovirus replication, including siRNA or drugs. Here, we tested whether stable expression of shRNA designed to target hexon, Iva2, or pol can inhibit the replication of a recombinant adenoviral vector, Ad-LacZ (serotype 5, E1/E3 deleted), in 293T cells. Significant knockdown correlating with reduced Ad-LacZ replication was achieved only when hexon was targeted. Cell sorting and isolation of cellular clones further accentuated knockdown of the hexon transcript, reduced protein levels by more than 90%, and diminished adenovirus production. As visualized by transmission electron microscopy, the cellular clone expressing the hexon-specific shRNA yielded 89.2% fewer particles compared to the parental 293T cells. Full scale production followed by purification revealed a 90.2% reduction in Ad-LacZ biological titer. These results support the notion that stable expression of shRNA can be used as a means to control adenovirus replication.
- Perspectives for Combining Viral Oncolysis With Additional Immunotherapies for the Treatment of Melanoma(2022) CERQUEIRA, Otto Luiz Dutra; ANTUNES, Fernanda; ASSIS, Nadine G.; CARDOSO, Elaine C.; CLAVIJO-SALOMON, Maria A.; DOMINGUES, Ana C.; TESSAROLLO, Nayara G.; STRAUSS, Bryan E.Melanoma is the deadliest type of skin cancer with steadily increasing incidence worldwide during the last few decades. In addition to its tumor associated antigens (TAAs), melanoma has a high mutation rate compared to other tumors, which promotes the appearance of tumor specific antigens (TSAs) as well as increased lymphocytic infiltration, inviting the use of therapeutic tools that evoke new or restore pre-existing immune responses. Innovative therapeutic proposals, such as immune checkpoint inhibitors (ICIs), have emerged as effective options for melanoma. However, a significant portion of these patients relapse and become refractory to treatment. Likewise, strategies using viral vectors, replicative or not, have garnered confidence and approval by different regulatory agencies around the world. It is possible that further success of immune therapies against melanoma will come from synergistic combinations of different approaches. In this review we outline molecular features inherent to melanoma and how this supports the use of viral oncolysis and immunotherapies when used as monotherapies or in combination.
- Induction of Immune-Stimulating Factors and Oncolysis Upon p14(ARF) Gene Transfer in Melanoma Cell Lines(2023) MENDONCA, Samir Andrade; ANTUNES, Fernanda; CERQUEIRA, Otto L. D.; VALLE, Paulo Roberto Del; HUNGER, Aline; OLIVEIRA, Percillia V. S. de; BRITO, Barbara; COSTANZI-STRAUSS, Eugenia; STRAUSS, Bryan E.Together with an anti-tumor immune response, oncolysis using a recombinant viral vector promises to eliminate cancer cells by both gene transfer and host-mediated functions. In this study we explore oncolysis induced by nonreplicating adenoviral vectors used for p14(ARF) and interferon-beta (hIFN beta) gene transfer in human melanoma cell lines, revealing an unexpected role for p14(ARF) in promoting cellular responses predictive of immune stimulation. Oncolysis was confirmed when UACC-62 (p53 wild-type) cells succumbed upon p14(ARF) gene transfer in vitro, whereas SK-Mel-29 (p53-mutant) benefitted from its combination with hIFN beta. In the case of UACC-62, in situ gene therapy in nude mice yielded reduced tumor progression in response to the p14(ARF) and hIFN beta combination. Potential for immune stimulation was revealed where p14(ARF) gene transfer in vitro was sufficient to induce emission of immunogenic cell death factors in UACC-62 and upregulate pro-immune genes, including IRF1, IRF7, IRF9, ISG15, TAP-1, and B2M. In SK-Mel-29, p14(ARF) gene transfer induced a subset of these factors. hIFN beta was, as expected, sufficient to induce these immune-stimulating genes in both cell lines. This work is a significant advancement for our melanoma gene therapy strategy because we revealed not only the induction of oncolysis, but also the potential contribution of p14(ARF) to immune stimulation.