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1.
Urol Clin North Am ; 47(4): 413-417, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008492

RESUMO

In recent years, immunotherapy has been the focus of great interest to researchers, clinicians, and the general public. Traditionally cancer therapy has been thought to be limited to surgery, radiation therapy, or chemotherapy. Some clinicians have considered it the so-called fifth pillar of cancer therapy, following surgery, cytotoxic chemotherapy, radiation, and targeted therapy. However, the origins of immunotherapy in cancer treatment reach back at least into the nineteenth century. This article reviews the origins, development, and future of immunotherapy.


Assuntos
Fatores Imunológicos/administração & dosagem , Imunoterapia/métodos , Neoplasias Urológicas/imunologia , Neoplasias Urológicas/terapia , História do Século XIX , Humanos , Imunoterapia/história , Estados Unidos , Neoplasias Urológicas/patologia
2.
Urol Clin North Am ; 47(4): 419-431, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008493

RESUMO

The management of metastatic renal cell carcinoma (RCC) has evolved rapidly in recent years with several immunotherapy-based combinations of strategies approved as first-line therapies. Targeted strategies, including systemic antiangiogenesis agents and immune checkpoint blockade, form the basis of a therapeutic approach. With rising rates of recurrence after first-line treatment, it is increasingly important to not only adopt a personalized treatment plan with minimal adverse events but also develop predictive biomarkers for response. This review discusses currently available first-line and second-line therapies in RCC and their pivotal data, with specific focus on ongoing clinical trials in the adjuvant setting, including those involving novel agents.


Assuntos
Produtos Biológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Imunoterapia/métodos , Neoplasias Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Ensaios Clínicos Fase II como Assunto , Terapia Combinada , Quimioterapia Combinada , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Nefrectomia/métodos , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
3.
Urol Clin North Am ; 47(4): 433-442, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008494

RESUMO

Natural killer (NK) cells are potently cytolytic innate lymphocytes involved in the immune surveillance of tumors and virally infected cells. Although much progress has been made in manipulating the ability of T cells to recognize and eliminate tumors, a comprehensive understanding of NK-cell infiltration into solid tumors, and their amenability to immunomodulation, remains incomplete. This article discusses recent studies showing that urologic tumors are infiltrated by NK cells and that these NK cells are often dysfunctional, but that strategies interfering with inhibitory axes have significant potential to alleviate this dysfunction.


Assuntos
Imunoterapia/métodos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Terapia de Alvo Molecular/métodos , Neoplasias Urogenitais/terapia , Terapia Biológica/métodos , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Neoplasias Renais/imunologia , Neoplasias Renais/terapia , Masculino , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/terapia , Medição de Risco , Resultado do Tratamento , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias Urogenitais/imunologia
4.
Urol Clin North Am ; 47(4): 443-456, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008495

RESUMO

Cancer vaccines, cytokines, and checkpoint inhibitors are immunotherapeutic agents that act within the cancer immunity cycle. Prostate cancer has provided unique opportunities for, and challenges to, immunotherapy drug development, including low tumor mutational burdens, limited expression of PD-L1, and minimal T-cell intratumoral infiltrates. Nevertheless, efforts are ongoing to help prime prostate tumors by turning a "cold" prostate cancer "hot" and thus rendering them more susceptible to immunotherapy. Combination treatments, use of molecular biomarkers, and use of new immunotherapeutic agents provide opportunities to enhance the immune response to prostate tumors.


Assuntos
Vacinas Anticâncer/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Idoso , Biomarcadores Tumorais/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/mortalidade , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
5.
Urol Clin North Am ; 47(4): 457-467, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008496

RESUMO

Biochemically recurrent prostate cancer represents a stage of prostate cancer where conventional (continued on next page) computed tomography and technetium Tc 99m bone scan imaging are unable to detect disease after curative intervention despite rising prostate-specific antigen. There is no clear standard of care and no systemic therapy has been shown to improve survival. Immunotherapy-based treatments potentially are attractive options relative to androgen deprivation therapy due to the generally more favorable side-effect profile. Biochemically recurrent prostate cancer patients have a low tumor burden and likely lymph node-based disease, which may make them more likely to respond to immunotherapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Imunoterapia/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias da Próstata/patologia , Idoso , Terapia Combinada , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Seleção de Pacientes , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Medição de Risco , Papel (figurativo) , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
6.
Urol Clin North Am ; 47(4): 469-474, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008497

RESUMO

Multiple immunologic platforms have provided minimal impact in patients with metastatic castration-resistant prostate cancer, necessitating that novel approaches continue to be developed. Although checkpoint inhibitors have been largely ineffective, there remain small cohorts of patients who have durable responses but lack the conventional indicators for response to this class of drugs, that is, high mutational burden or significant genomic alterations, as seen in other solid tumors. This article presents an update on the evolution of immunotherapeutics that target a more lethal form of prostate cancer and provides the groundwork for future considerations as to how this field should proceed.


Assuntos
Quinases Ciclina-Dependentes/genética , Regulação Neoplásica da Expressão Gênica , Imunoterapia/métodos , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/terapia , Idoso , Produtos Biológicos/uso terapêutico , Vacinas Anticâncer/administração & dosagem , Quinases Ciclina-Dependentes/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Fenótipo , Medicina de Precisão/métodos , Prognóstico , Neoplasias de Próstata Resistentes à Castração/patologia , Análise de Sobrevida , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos
7.
Urol Clin North Am ; 47(4): 475-485, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008498

RESUMO

Cancer is a highly complex and heterogeneous disease and immunotherapy has shown promise as a therapeutic approach. The increased resolution afforded by single-cell analysis offers the hope of finding and characterizing previously underappreciated populations of cells that could prove useful in understanding cancer progression and treatment. Urologic and prostate cancers are inherently heterogeneous diseases, and the potential for single-cell analysis to help understand and develop immunotherapeutic approaches to treat these diseases is very exciting. In this review, we view cancer immunotherapy through a single-cell lens and discuss the state-of-the-art technologies that enable advances in this field.


Assuntos
Imunoterapia/métodos , Terapia de Alvo Molecular/métodos , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Microambiente Tumoral/efeitos dos fármacos , Feminino , Previsões , Humanos , Masculino , Terapia de Alvo Molecular/tendências , Prognóstico , Neoplasias da Próstata/patologia , Medição de Risco , Análise de Sequência de DNA , Análise de Sequência de RNA , Análise de Célula Única , Resultado do Tratamento , Microambiente Tumoral/genética , Neoplasias Urológicas/genética , Neoplasias Urológicas/patologia , Neoplasias Urológicas/terapia
8.
Urol Clin North Am ; 47(4): 487-510, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008499

RESUMO

The advent of immunotherapy has revolutionized cancer treatment. Prostate cancer has an immunosuppressive microenvironment and a low tumor mutation burden, resulting in low neoantigen expression. The consensus was that immunotherapy would be less effective in prostate cancer. However, recent studies have reported that prostate cancer does have a high number of DNA damage and repair gene defects. Immunotherapies that have been tested in prostate cancer so far have been mainly vaccines and checkpoint inhibitors. A combination of genomically targeted therapies, with approaches to alleviate immune response and thereby make the tumor microenvironment immunologically hot, is promising.


Assuntos
Produtos Biológicos/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Imunoterapia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Microambiente Tumoral/efeitos dos fármacos , Idoso , Animais , Antígenos de Neoplasias/efeitos dos fármacos , Antígenos de Neoplasias/imunologia , Previsões , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Invasividade Neoplásica/patologia , Metástase Neoplásica/genética , Metástase Neoplásica/imunologia , Estadiamento de Neoplasias , Neoplasias da Próstata/genética , Resultado do Tratamento , Microambiente Tumoral/genética
9.
Urol Clin North Am ; 47(4): 511-521, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008500

RESUMO

The age of immuno-oncology has ushered in a rush within the biopharmaceutical industry. This intense focus has been characterized as a frenzy or overhyped, but represents a substantial investment in new products that hope to harness the immune system against cancer. Such agents include next-generation checkpoint antagonists, immune costimulatory agonists, and a diverse array of novel mechanisms of action and therapeutic modalities targeting immune cell types and the interplay of the host and tumor at the immune synapse. This article surveys the clinical development and investment activity with Immuno-Oncology, specifically prostate, kidney, and bladder cancers.


Assuntos
Produtos Biológicos/uso terapêutico , Biotecnologia/tendências , Imunoterapia/métodos , Microambiente Tumoral/efeitos dos fármacos , Neoplasias Urogenitais/imunologia , Neoplasias Urogenitais/terapia , Biotecnologia/métodos , Feminino , Previsões , Humanos , Masculino , Resultado do Tratamento , Microambiente Tumoral/imunologia , Neoplasias Urogenitais/mortalidade , Neoplasias Urogenitais/patologia
10.
Nat Commun ; 11(1): 4909, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999291

RESUMO

Effectively activating macrophages against cancer is promising but challenging. In particular, cancer cells express CD47, a 'don't eat me' signal that interacts with signal regulatory protein alpha (SIRPα) on macrophages to prevent phagocytosis. Also, cancer cells secrete stimulating factors, which polarize tumor-associated macrophages from an antitumor M1 phenotype to a tumorigenic M2 phenotype. Here, we report that hybrid cell membrane nanovesicles (known as hNVs) displaying SIRPα variants with significantly increased affinity to CD47 and containing M2-to-M1 repolarization signals can disable both mechanisms. The hNVs block CD47-SIRPα signaling axis while promoting M2-to-M1 repolarization within tumor microenvironment, significantly preventing both local recurrence and distant metastasis in malignant melanoma models. Furthermore, by loading a stimulator of interferon genes (STING) agonist, hNVs lead to potent tumor inhibition in a poorly immunogenic triple negative breast cancer model. hNVs are safe, stable, drug loadable, and suitable for genetic editing. These properties, combined with the capabilities inherited from source cells, make hNVs an attractive immunotherapy.


Assuntos
Micropartículas Derivadas de Células/imunologia , Imunoterapia/métodos , Macrófagos/imunologia , Melanoma/terapia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias de Mama Triplo Negativas/terapia , Animais , Antígeno CD47/metabolismo , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Melanoma/imunologia , Melanoma/secundário , Proteínas de Membrana/agonistas , Proteínas de Membrana/imunologia , Camundongos , Nanopartículas/administração & dosagem , Recidiva Local de Neoplasia/imunologia , Nucleotídeos Cíclicos/administração & dosagem , Receptores Imunológicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Neoplasias de Mama Triplo Negativas/imunologia , Evasão Tumoral/efeitos dos fármacos , Evasão Tumoral/imunologia , Microambiente Tumoral/imunologia
11.
Lancet Haematol ; 7(10): e765-e771, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32976753

RESUMO

Over the past 30 years, the scientific community has made little progress in changing the natural history of peripheral T-cell lymphomas. Of the haematological malignancies, T-cell lymphomas have an extremely poor prognosis. One reason for this poor outcome has been that no treatment programme has ever been developed specifically for the broader category of the disease-peripheral T-cell lymphoma-let alone any of the specific subtypes, except advances made for patients with CD30-positive anaplastic large cell lymphoma. Decades of effort have focused on retrofitting chemotherapy programmes used for other diseases, such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) for diffuse large B-cell lymphoma, which have not been associated with much progress, and have universally produced far more toxicity than benefit. A remarkable heterogeneity, a paucity of cases, and the absence of peripheral T-cell lymphoma-specific drugs, until recently at least, have limited the field's ability to make substantive and innovative advances. Over the past few years, however, it appears the field is beginning to make progress. Lineage and disease-specific novel-to-novel platforms are producing, although perhaps not unsurprisingly, compelling results suggesting that the path to a cure for this rare orphan disease might be heading in a different direction.


Assuntos
Linfoma de Células T Periférico/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Imunoterapia/métodos , Medicina de Precisão/métodos , Prednisona/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico
13.
Medicine (Baltimore) ; 99(37): e21788, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925716

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common neoplasms encountered, and its incidence is increasing worldwide. In this study, we explored the characteristics of gut microbiota in patients with primary hepatocellular carcinoma in advanced stage who received immune checkpoint inhibitors (ICIs) based on a large population with hepatitis B virus infection. An initial cohort of 65 patients with metastatic melanoma were included in this study. All patients were treated with ICIs at Fujian provincial geriatric hospital between August 2016 and June 2018. The 16S rDNA V4 region was amplified by Polymerase chain reaction and sequenced on the MiSeq platform. We found that the diversities of the gut microbiota in HCC who received ICIs were obviously increased. Negative feedback, which is controlled by interplay between microbial metabolic activities and host pathways, is thought to promote high bacterial diversity. We focused on the Faecalibacterium genus in response group, and Bacteroidales order in non-response group, and stratified patients into high versus low categories based on the median relative abundance of these taxa in the gut microbiome. Patients with high Faecalibacterium abundance had a significantly prolonged PFS versus those with a low abundance. Conversely, patients with a high abundance of Bacteroidales had a shortened progressive free survival compared to those with a low abundance. In summary, the present study examined the oral and gut microbiome of HCC patients undergoing immune checkpoint inhibitors immunotherapy. Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus non-responders.


Assuntos
Carcinoma Hepatocelular/microbiologia , Microbioma Gastrointestinal , Fatores Imunológicos/uso terapêutico , Imunoterapia/mortalidade , Neoplasias Hepáticas/microbiologia , Idoso , Bacteroides/crescimento & desenvolvimento , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , China , Faecalibacterium/crescimento & desenvolvimento , Feminino , Humanos , Imunoterapia/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , RNA Ribossômico 16S/análise , Resultado do Tratamento
14.
mBio ; 11(5)2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913009

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is a recently emerged respiratory coronavirus that has infected >23 million people worldwide with >800,000 deaths. Few COVID-19 therapeutics are available, and the basis for severe infections is poorly understood. Here, we investigated properties of type I (ß), II (γ), and III (λ1) interferons (IFNs), potent immune cytokines that are normally produced during infection and that upregulate IFN-stimulated gene (ISG) effectors to limit virus replication. IFNs are already in clinical trials to treat COVID-19. However, recent studies highlight the potential for IFNs to enhance expression of host angiotensin-converting enzyme 2 (ACE2), suggesting that IFN therapy or natural coinfections could exacerbate COVID-19 by upregulating this critical virus entry receptor. Using a cell line model, we found that beta interferon (IFN-ß) strongly upregulated expression of canonical antiviral ISGs, as well as ACE2 at the mRNA and cell surface protein levels. Strikingly, IFN-λ1 upregulated antiviral ISGs, but ACE2 mRNA was only marginally elevated and did not lead to detectably increased ACE2 protein at the cell surface. IFN-γ induced the weakest ISG response but clearly enhanced surface expression of ACE2. Importantly, all IFN types inhibited SARS-CoV-2 replication in a dose-dependent manner, and IFN-ß and IFN-λ1 exhibited potent antiviral activity in primary human bronchial epithelial cells. Our data imply that type-specific mechanisms or kinetics shape IFN-enhanced ACE2 transcript and cell surface levels but that the antiviral action of IFNs against SARS-CoV-2 counterbalances any proviral effects of ACE2 induction. These insights should aid in evaluating the benefits of specific IFNs, particularly IFN-λ, as repurposed therapeutics.IMPORTANCE Repurposing existing, clinically approved, antiviral drugs as COVID-19 therapeutics is a rapid way to help combat the SARS-CoV-2 pandemic. Interferons (IFNs) usually form part of the body's natural innate immune defenses against viruses, and they have been used with partial success to treat previous new viral threats, such as HIV, hepatitis C virus, and Ebola virus. Nevertheless, IFNs can have undesirable side effects, and recent reports indicate that IFNs upregulate the expression of host ACE2 (a critical entry receptor for SARS-CoV-2), raising the possibility that IFN treatments could exacerbate COVID-19. Here, we studied the antiviral- and ACE2-inducing properties of different IFN types in both a human lung cell line model and primary human bronchial epithelial cells. We observed differences between IFNs with respect to their induction of antiviral genes and abilities to enhance the cell surface expression of ACE2. Nevertheless, all the IFNs limited SARS-CoV-2 replication, suggesting that their antiviral actions can counterbalance increased ACE2.


Assuntos
Antivirais/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Interferon Tipo I/farmacologia , Interferon gama/farmacologia , Interferons/farmacologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Idoso , Animais , Betacoronavirus/imunologia , Linhagem Celular , Chlorocebus aethiops , Feminino , Humanos , Imunoterapia/métodos , Interferon Tipo I/efeitos adversos , Interferon gama/efeitos adversos , Interferons/efeitos adversos , Pandemias , Peptidil Dipeptidase A/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores Virais/metabolismo , Mucosa Respiratória/citologia , Mucosa Respiratória/virologia , Regulação para Cima/efeitos dos fármacos , Células Vero , Replicação Viral/efeitos dos fármacos
15.
Nat Commun ; 11(1): 4840, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973129

RESUMO

Immunotherapies revolutionized cancer treatment by harnessing the immune system to target cancer cells. However, most patients are resistant to immunotherapies and the mechanisms underlying this resistant is still poorly understood. Here, we report that overexpression of BMP7, a member of the TGFB superfamily, represents a mechanism for resistance to anti-PD1 therapy in preclinical models and in patients with disease progression while on immunotherapies. BMP7 secreted by tumor cells acts on macrophages and CD4+ T cells in the tumor microenvironment, inhibiting MAPK14 expression and impairing pro-inflammatory responses. Knockdown of BMP7 or its neutralization via follistatin in combination with anti-PD1 re-sensitizes resistant tumors to immunotherapies. Thus, we identify the BMP7 signaling pathway as a potential immunotherapeutic target in cancer.


Assuntos
Proteína Morfogenética Óssea 7/genética , Proteína Morfogenética Óssea 7/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Imunoterapia/métodos , Neoplasias/metabolismo , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Linfócitos T CD4-Positivos , Linhagem Celular Tumoral , Feminino , Folistatina/metabolismo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Proteína Quinase 14 Ativada por Mitógeno/genética , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Receptor de Morte Celular Programada 1/efeitos dos fármacos , Células RAW 264.7 , Proteína Smad1/metabolismo , Transcriptoma , Microambiente Tumoral/efeitos dos fármacos
17.
Anticancer Res ; 40(10): 5765-5776, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988904

RESUMO

BACKGROUND/AIM: We evaluated the safety, feasibility, and preliminary efficacy of Wilms tumor gene 1 (WT1) peptide and Mucin 1 (MUC1)-pulsed dendritic cell (DC) (WT1/MUC1-DC) vaccination as an adjuvant immunotherapy for surgically resectable pancreatic ductal adenocarcinoma (PDA) patients. PATIENTS AND METHODS: Eligible patients were administered WT1/MUC1-DC vaccination at least seven times every 2 weeks with concomitant adjuvant chemotherapy after surgical resection of PDA. RESULTS: Ten patients were enrolled and no Grade 2 or higher toxicities were associated with DC vaccination. The estimated overall survival (OS) and relapse-free survival (RFS) at 3-years from the time of surgical resection were 77.8% and 35.0%, respectively. Immunohistochemical analysis suggested a possible relationship between induction of WT1-specific cytotoxic T lymphocyte after DC vaccination and higher infiltration of CD3/CD4/CD8 lymphocytes in tumor tissues. CONCLUSION: WT1/MUC1-DC vaccination in the adjuvant setting was safe and well-tolerated in PDA patients after tumor resection. A large-scale prospective study is warranted to evaluate the clinical benefit of this modality.


Assuntos
Adenocarcinoma/tratamento farmacológico , Carcinoma Ductal Pancreático/tratamento farmacológico , Mucina-1/genética , Proteínas WT1/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Quimioterapia Adjuvante/métodos , Células Dendríticas/imunologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Humanos , Imunoterapia/métodos , Masculino , Pessoa de Meia-Idade , Mucina-1/uso terapêutico , Proteínas WT1/uso terapêutico
18.
Int J Mol Sci ; 21(16)2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32824753

RESUMO

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 and its associated pathology, COVID-19, have been of particular concerns these last months due to the worldwide burden they represent. The number of cases requiring intensive care being the critical point in this epidemic, a better understanding of the pathophysiology leading to these severe cases is urgently needed. Tissue lesions can be caused by the pathogen or can be driven by an overwhelmed immune response. Focusing on SARS-CoV-2, we and others have observed that this virus can trigger indeed an immune response that can be dysregulated in severe patients and leading to further injury to multiple organs. The purpose of the review is to bring to light the current knowledge about SARS-CoV-2 virologic and immunologic features. Thus, we address virus biology, life cycle, tropism for many organs and how ultimately it will affect several host biological and physiological functions, notably the immune response. Given that therapeutic avenues are now highly warranted, we also discuss the immunotherapies available to manage the infection and the clinical outcomes.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Fatores Etários , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/terapia , Citocinas/sangue , Humanos , Imunoterapia/métodos , Pulmão/patologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/terapia , RNA Replicase/metabolismo , Proteínas não Estruturais Virais/metabolismo , Tropismo Viral/fisiologia , Montagem de Vírus/fisiologia , Replicação Viral/fisiologia
19.
Cell Transplant ; 29: 963689720952089, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32830527

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic, originating from Wuhan, China, is known to cause severe acute respiratory symptoms. The occurrence of a cytokine storm in the lungs is a critical step in the disease pathogenesis, as it causes pathological lesions, pulmonary edema, and acute respiratory distress syndrome, potentially resulting in death. Currently, there is no effective treatment that targets the cytokine storm and helps regenerate the damaged tissue. Mesenchymal stem cells (MSCs) are known to act as anti-inflammatory/immunomodulatory candidates and activate endogenous regeneration. As a result, MSC therapy is a potential treatment approach for COVID-19. Intravenous injection of clinical-grade MSCs into COVID-19 patients can induce an immunomodulatory response along with improved lung function. Dental pulp stem cells (DPSCs) are considered a potential source of MSCs for immunomodulation, tissue regeneration, and clinical application. Although some current clinical trials have treated COVID-19 patients with DPSCs, this therapy has not been approved. Here, we review the potential use of DPSCs and their significance in the development of a therapy for COVID-19.


Assuntos
Infecções por Coronavirus/terapia , Polpa Dentária/citologia , Imunomodulação , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Pneumonia Viral/terapia , Betacoronavirus/imunologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Polpa Dentária/imunologia , Humanos , Imunoterapia/métodos , Inflamação/imunologia , Inflamação/terapia , Pulmão/imunologia , Pulmão/fisiologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/terapia , Células-Tronco Mesenquimais/citologia , Pandemias , Pneumonia Viral/imunologia , Regeneração
20.
Expert Opin Biol Ther ; 20(9): 1033-1046, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32744917

RESUMO

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has spread to several countries globally. Currently, there is no specific drug or vaccine available for managing COVID-19. Antibody-based immunotherapeutic strategies using convalescent plasma, monoclonal antibodies (mAbs), neutralizing antibodies (NAbs), and intravenous immunoglobulins have therapeutic potential. AREAS COVERED: This review provides the current status of the development of various antibody-based immunotherapeutics such as convalescent plasma, mAbs, NAbs, and intravenous immunoglobulins against COVID-19. The review also highlights their advantages, disadvantages, and clinical utility for the treatment of COVID-19 patients. EXPERT OPINION: In a pandemic situation such as COVID-19, the development of new drugs should focus on and expedite the strategies where safety and efficacy are proven. Antibody-based immunotherapeutic approaches such as convalescent plasma, intravenous immunoglobulins, and mAbs have a proven record of safety and efficacy and are in use for decades. Some of them are already being used to manage COVID-19 patients and found to be useful. However, the mAbs with virus neutralization potential is the need of the hour during this COVID-19 pandemic to be more specific and virus targeted. The research and investment need to be accelerated to bring them into clinical use for prophylactic and therapeutic purposes against COVID-19.


Assuntos
Betacoronavirus , Imunoglobulinas Intravenosas/uso terapêutico , Imunoterapia/métodos , Anticorpos Neutralizantes/uso terapêutico , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Humanos , Imunização Passiva , Imunoglobulinas Intravenosas/imunologia , Imunoterapia/tendências , Pandemias/prevenção & controle , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Pneumonia Viral/terapia
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