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
20 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 20
- Overhauling CAR T Cells to Improve Efficacy, Safety and Cost(2020) CHICAYBAM, Leonardo; BONAMINO, Martin H.; INVITTI, Adriana Luckow; ROZENCHAN, Patricia Bortman; VIEIRA, Igor de Luna; STRAUSS, Bryan E.Gene therapy is now surpassing 30 years of clinical experience and in that time a variety of approaches has been applied for the treatment of a wide range of pathologies. While the promise of gene therapy was over-stated in the 1990's, the following decades were met with polar extremes between demonstrable success and devastating setbacks. Currently, the field of gene therapy is enjoying the rewards of overcoming the hurdles that come with turning new ideas into safe and reliable treatments, including for cancer. Among these modalities, the modification of T cells with chimeric antigen receptors (CAR-T cells) has met with clear success and holds great promise for the future treatment of cancer. We detail a series of considerations for the improvement of the CAR-T cell approach, including the design of the CAR, routes of gene transfer, introduction of CARs in natural killer and other cell types, combining the CAR approach with checkpoint blockade or oncolytic viruses, improving pre-clinical models as well as means for reducing cost and, thus, making this technology more widely available. While CAR-T cells serve as a prime example of translating novel ideas into effective treatments, certainly the lessons learned will serve to accelerate the current and future development of gene therapy drugs.
- GENE THERAPY WITH P19ARF AND INTERFERON-BETA SENSITIZES CELLS TO PD-1 CHECKPOINT BLOCKADE AND ENHANCES ANTITUMOR IMMUNE RESPONSES IN RESISTANT MOUSE MODELS(2022) DOMINGUES, Ana; TESSAROLLO, Nayara; STRAUSS, Bryan
- Interferons: key modulators of the immune system in cancer(2023) YUSUF, Nabiha; ALLIE, S. Rameeza; STRAUSS, Bryan E.
- Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma(2017) EUGENIO, Angela Isabel Pereira; FOOK-ALVES, Veruska Lia; OLIVEIRA, Mariana Bleker de; FERNANDO, Rodrigo Carlini; ZANATTA, Daniela B.; STRAUSS, Bryan Eric; SILVA, Maria Regina Regis; PORCIONATTO, Marimelia Aparecida; COLLEONI, Gisele Wally BragaHSP70 connects multiple signaling pathways that work synergistically to protect tumor cells from death by proteotoxic stress and represents a possible target to establish a new approach for multiple myeloma treatment. Therefore, bioluminescent cell lines RPMI8226-LUC-PURO and U266-LUC-PURO were treated with HSP70 (VER155008) and/or proteasome (bortezomib) inhibitors and immunodeficient mice were used for subcutaneous xenograft models to evaluate tumor growth reduction and tumor growth inhibition after treatment. Bioluminescence imaging was used to follow tumor response. Treatment with bortezomib showed similar to 60% of late apoptosis in RPMI8226-LUC-PURO (without additional benefit of VER155008 in this cell line). However, U266-LUC-PURO showed similar to 60% of cell death after treatment with VER155008 (alone or with bortezomib). RPMI8226-LUC-PURO xenograft presented tumor reduction by bioluminescence imaging after treatment with bortezomib, VER155008 or drug combination compared to controls. Treatment with bortezomib, alone or combined with VER155008, showed inhibition of tumor growth assessed by bioluminescence imaging after one week in both RPMI8226-LUC-PURO and U266-LUC-PURO cell lines when compared to controls. In conclusion, our study shows that the combination of proteasome and HSP70 inhibitors induced cell death in tumor cells in vitro (late apoptosis induction) and in vivo (inhibition of tumor growth) with special benefit in U266-LUC-PURO, bearing 17p deletion.
- Protein Disulfide Isomerase overexpression induces mitochondrial reorganization and a differentiated VSMC phenotype: role of mitofusin-2(2023) WOSNIAK JR., Joao; RODRIGUES, Rafael F. G.; KAKIMOTO, Pamela A.; SILVA, Camille C. Caldeira da; ANTUNES, Fernanda; STRAUSS, Bryan E.; KOWALTOWSKI, Alicia; LAURINDO, Francisco R.
- Intratumoral Immunization by p19Arf and Interferon-beta Gene Transfer in a Heterotopic Mouse Model of Lung Carcinoma(2016) CATANI, Joao Paulo Portela; MEDRANO, Ruan F. V.; HUNGER, Aline; VALLE, Paulo Del; ADJEMIAN, Sandy; ZANATTA, Daniela Bertolini; KROEMER, Guido; COSTANZI-STRAUSS, Eugenia; STRAUSS, Bryan E.Therapeutic strategies that act by eliciting and enhancing antitumor immunity have been clinically validated as an effective treatment modality but may benefit from the induction of both cell death and immune activation as primary stimuli. Using our AdRGD-PG adenovector platform, we show here for the first time that in situ gene transfer of p19Arf and interferon-beta (IFN beta) in the LLC1 mouse model of lung carcinoma acts as an immunotherapy. Although p19Arf is sufficient to induce cell death, only its pairing with IFN beta significantly inducedmarkers of immunogenic cell death. In situ gene therapy with IFN beta, either alone or in combination with p19Arf, could retard tumor progression, but only the combined treatment was associated with a protective immune response. Specifically in the case of combined intratumoral gene transfer, we identified 167 differentially expressed genes when usingmicroarray to evaluate tumors that were treated in vivo and confirmed the activation of CCL3, CXCL3, IL1 alpha, IL1 beta, CD274, and OSM, involved in immune response and chemotaxis. Histologic evaluation revealed significant tumor infiltration by neutrophils, whereas functional depletion of granulocytes ablated the antitumor effect of our approach. The association of in situ gene therapy with cisplatin resulted in synergistic elimination of tumor progression. In all, in situ gene transfer with p19Arf and IFN beta acts as an immunotherapy involving recruitment of neutrophils, a desirable but previously untested outcome, and this approach may be allied with chemotherapy, thus providing significant antitumor activity and warranting further development for the treatment of lung carcinoma.
conferenceObject Membrane coating for nonreplicating adenoviral vectors aids gene delivery in a murine model of melanoma(2021) TESSAROLLO, N. G.; DOMINGUES, A. C. M.; STRAUSS, B. 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.
- Uncovering the immunotherapeutic cycle initiated by p19Arf and interferon-beta gene transfer to cancer cells: An inducer of immunogenic cell death(2017) MEDRANO, Ruan F. V.; HUNGER, Aline; CATANI, Joao P. P.; STRAUSS, Bryan E.Simultaneous reestablishment of p53/p19(Arf) and interferon-beta pathways in melanoma cells culminates in a cell death process that displays features of necroptosis along with the release of immunogenic cell death molecules and unleashes an antitumor immune response mediated by natural killer cells, neutrophils as well as CD4(+) and CD8(+) T lymphocytes.
conferenceObject Induction of immunogenic cell death in a canine melanoma model in response to p14ARF and interferon-beta co-transduction by adenoviral vectors(2022) RODRIGUES, O. A.; STRAUSS, B. E.