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
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- Consensus guidelines for the definition, detection and interpretation of immunogenic cell death(2020) GALLUZZI, Lorenzo; VITALE, Ilio; WARREN, Sarah; ADJEMIAN, Sandy; AGOSTINIS, Patrizia; MARTINEZ, Aitziber Buque; CHAN, Timothy A.; COUKOS, George; DEMARIA, Sandra; DEUTSCH, Eric; DRAGANOV, Dobrin; EDELSON, Richard L.; FORMENTI, Silvia C.; FUCIKOVA, Jitka; GABRIELE, Lucia; GAIPL, Udo S.; GAMEIRO, Sofia R.; GARG, Abhishek D.; GOLDEN, Encouse; HAN, Jian; HARRINGTON, Kevin J.; HEMMINKI, Akseli; HODGE, James W.; HOSSAIN, Dewan Md Sakib; ILLIDGE, Tim; KARIN, Michael; KAUFMAN, Howard L.; KEPP, Oliver; KROEMER, Guido; LASARTE, Juan Jose; LOI, Sherene; LOTZE, Michael T.; MANIC, Gwenola; MERGHOUB, Taha; MELCHER, Alan A.; MOSSMAN, Karen L.; PROSPER, Felipe; REKDAL, Oystein; RESCIGNO, Maria; RIGANTI, Chiara; SISTIGU, Antonella; SMYTH, Mark J.; SPISEK, Radek; STAGG, John; STRAUSS, Bryan E.; TANG, Daolin; TATSUNO, Kazuki; GOOL, Stefaan W. van; VANDENABEELE, Peter; YAMAZAKI, Takahiro; ZAMARIN, Dmitriy; ZITVOGEL, Laurence; CESANO, Alessandra; MARINCOLA, Francesco M.Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.
- 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.
- Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy(2017) MEDRANO, Ruan F. V.; HUNGER, Aline; MENDONCA, Samir Andrade; BARBUTO, Jose Alexandre M.; STRAUSS, Bryan E.During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-alpha and IFN-beta, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-alpha/beta share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular phenotypes. For example, type I IFNs drive not only the high maturation status of DCs, but also have a direct impact in cytotoxic T lymphocytes, NK cell activation, induction of tumor cell death and inhibition of angiogenesis. A variety of stimuli, including some standard cancer treatments, promote the expression of endogenous IFN-alpha/beta, which then participates as a fundamental component of immunogenic cell death. Systemic treatment with recombinant protein has been used for the treatment of melanoma. The induction of endogenous IFN-alpha/beta has been tested, including stimulation through pattern recognition receptors. Gene therapies involving IFN-alpha/beta have also been described. Thus, harnessing type I IFNs as an effective tool for cancer therapy continues to be studied.
- Perspectives for cancer immunotherapy mediated by p19Arf plus interferon-beta gene transfer(2018) STRAUSS, Bryan E.; SILVA, Gissele Rolemberg Oliveira; VIEIRA, Igor de Luna; CERQUEIRA, Otto Luiz Dutra; VALLE, Paulo Roberto Del; MEDRANO, Ruan Felipe Vieira; MENDONCA, Samir AndradeWhile cancer immunotherapy has gained much deserved attention in recent years, many areas regarding the optimization of such modalities remain unexplored, including the development of novel approaches and the strategic combination of therapies that target multiple aspects of the cancer-immunity cycle. Our own work involves the use of gene transfer technology to promote cell death and immune stimulation. Such immunogenic cell death, mediated by the combined transfer of the alternate reading frame (p14ARF in humans and p19Arf in mice) and the interferon-beta cDNA in our case, was shown to promote an antitumor immune response in mouse models of melanoma and lung carcinoma. With these encouraging results, we are now setting out on the road toward translational and preclinical development of our novel immunotherapeutic approach. Here, we outline the perspectives and challenges that we face, including the use of human tumor and immune cells to verify the response seen in mouse models and the incorporation of clinically relevant models, such as patient-derived xenografts and spontaneous tumors in animals. In addition, we seek to combine our immunotherapeutic approach with other treatments, such as chemotherapy or checkpoint blockade, with the goal of reducing dosage and increasing efficacy. The success of any translational research requires the cooperation of a multidisciplinary team of professionals involved in laboratory and clinical research, a relationship that is fostered at the Cancer Institute of Sao Paulo.
- Improving adenoviral vectors and strategies for prostate cancer gene therapy(2018) TAMURA, Rodrigo Esaki; LUNA, Igor Vieira de; LANA, Marlous Gomes; STRAUSS, Bryan E.Gene therapy has been evaluated for the treatment of prostate cancer and includes the application of adenoviral vectors encoding a suicide gene or oncolytic adenoviruses that may be armed with a functional transgene. In parallel, versions of adenoviral vector expressing the p53 gene (Ad-p53) have been tested as treatments for head and neck squamous cell carcinoma and non-small cell lung cancer. Although Ad-p53 gene therapy has yielded some interesting results when applied to prostate cancer, it has not been widely explored, perhaps due to current limitations of the approach. To achieve better functionality, improvements in the gene transfer system and the therapeutic regimen may be required. We have developed adenoviral vectors whose transgene expression is controlled by a p53-responsive promoter, which creates a positive feedback mechanism when used to drive the expression of p53. Together with improvements that permit efficient transduction, this new approach was more effective than the use of traditional versions of Ad-p53 in killing prostate cancer cell lines and inhibiting tumor progression. Even so, gene therapy is not expected to replace traditional chemotherapy but should complement the standard of care. In fact, chemotherapy has been shown to assist in viral transduction and transgene expression. The cooperation between gene therapy and chemotherapy is expected to effectively kill tumor cells while permitting the use of reduced chemotherapy drug concentrations and, thus, lowering side effects. Therefore, the combination of gene therapy and chemotherapy may prove essential for the success of both approaches.
- New routes for transgenesis of the mouse(2012) BELIZARIO, Jose E.; AKAMINI, Priscilla; WOLF, Philip; STRAUSS, Bryan; XAVIER-NETO, JoseTransgenesis refers to the molecular genetic techniques for directing specific insertions, deletions and point mutations in the genome of germ cells in order to create genetically modified organisms (GMO). Genetic modification is becoming more practicable, efficient and predictable with the development and use of a variety of cell and molecular biology tools and DNA sequencing technologies. A collection of plasmidial and viral vectors, cell-type specific promoters, positive and negative selectable markers, reporter genes, drug-inducible Cre-loxP and Flp/FRT recombinase systems are available which ensure efficient transgenesis in the mouse. The technologies for the insertion and removal of genes by homologous-directed recombination in embryonic stem cells (ES) and generation of targeted gain- and loss-of function alleles have allowed the creation of thousands of mouse models of a variety of diseases. The engineered zinc finger nucleases (ZFNs) and small hairpin RNA-expressing constructs are novel tools with useful properties for gene knockout free of ES manipulation. In this review we briefly outline the different approaches and technologies for transgenesis as well as their advantages and disadvantages. We also present an overview on how the novel integrative mouse and human genomic databases and bioinformatics approaches have been used to understand genotype-phenotype relationships of hundreds of mutated and candidate disease genes in mouse models. The updating and continued improvements of the genomic technologies will eventually help us to unraveling the biological and pathological processes in such a way that they can be translated more efficiently from mouse to human and vise-versa.
- 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.
- Clinical Applications and Immunological Aspects of Electroporation-Based Therapies(2021) LUZ, Jean Carlos dos Santos da; ANTUNES, Fernanda; CLAVIJO-SALOMON, Maria Alejandra; SIGNORI, Emanuela; TESSAROLLO, Nayara Gusmao; STRAUSS, Bryan E.Reversible electropermeabilization (RE) is an ultrastructural phenomenon that transiently increases the permeability of the cell membrane upon application of electrical pulses. The technique was described in 1972 by Neumann and Rosenheck and is currently used in a variety of applications, from medicine to food processing. In oncology, RE is applied for the intracellular transport of chemotherapeutic drugs as well as the delivery of genetic material in gene therapies and vaccinations. This review summarizes the physical changes of the membrane, the particularities of bleomycin, and the immunological aspects involved in electrochemotherapy and gene electrotransfer, two important EP-based cancer therapies in human and veterinary oncology.
- Nonreplicating Adenoviral Vectors: Improving Tropism and Delivery of Cancer Gene Therapy(2021) TESSAROLLO, Nayara Gusmao; DOMINGUES, Ana Carolina M.; ANTUNES, Fernanda; LUZ, Jean Carlos dos Santos da; RODRIGUES, Otavio Augusto; CERQUEIRA, Otto Luiz Dutra; STRAUSS, Bryan E.Simple Summary The treatment of cancer has progressed greatly with the advent of immunotherapy and gene therapy, including the use of nonreplicating adenoviral vectors to deliver genes with antitumor activity for cancer gene therapy. Even so, the successful application of these vectors may benefit from modifications in their design, including their molecular structure, so that specificity for the target cell is increased and off-target effects are minimized. With such improvements, we may find new opportunities for systemic administration of adenoviral vectors as well as the delivery of strategic antigen targets of an antitumor immune response. We propose that the improvement of nonreplicating adenoviral vectors will allow them to continue to hold a key position in cancer gene therapy and immunotherapy. Recent preclinical and clinical studies have used viral vectors in gene therapy research, especially nonreplicating adenovirus encoding strategic therapeutic genes for cancer treatment. Adenoviruses were the first DNA viruses to go into therapeutic development, mainly due to well-known biological features: stability in vivo, ease of manufacture, and efficient gene delivery to dividing and nondividing cells. However, there are some limitations for gene therapy using adenoviral vectors, such as nonspecific transduction of normal cells and liver sequestration and neutralization by antibodies, especially when administered systemically. On the other hand, adenoviral vectors are amenable to strategies for the modification of their biological structures, including genetic manipulation of viral proteins, pseudotyping, and conjugation with polymers or biological membranes. Such modifications provide greater specificity to the target cell and better safety in systemic administration; thus, a reduction of antiviral host responses would favor the use of adenoviral vectors in cancer immunotherapy. In this review, we describe the structural and molecular features of nonreplicating adenoviral vectors, the current limitations to their use, and strategies to modify adenoviral tropism, highlighting the approaches that may allow for the systemic administration of gene therapy.