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2.
Jpn J Clin Oncol ; 50(11): 1231-1245, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-32984905

RESUMO

Treatment and resolution of primary and metastatic brain tumors have long presented a challenge to oncologists. In response to the dismal survival outcomes associated with conventional therapies, various immunotherapy modalities, such as checkpoint inhibitors, vaccine, cellular immunotherapy and viral immunotherapy have been actively explored over the past couple of decades. Although improved patient survival has been more frequently noted in treatment of brain metastases, little progress has been made in improving patient survival in cases of primary brain tumors, specifically glioblastoma, which is the representative primary brain tumor discussed in this review. Herein, we will first overview the findings of recent clinical studies for treatment of primary and metastatic brain tumors with immunotherapeutic interventions. The clinical efficacy of these immunotherapies will be discussed in the context of their ability or inability to overcome inherent characteristics of the tumor as well as restricted antigen presentation and its immunosuppressive microenvironment. Additionally, this review aims to briefly inform clinicians in the field of neuro-oncology on the relevant aspects of the immune system as it pertains to the central nervous system, with special focus on the differing modes of antigen presentation and tumor microenvironment of primary and metastatic brain tumors and the role these differences may play in the efficacy of immunotherapy in eradicating the tumor.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Imunoterapia/tendências , Neoplasias Encefálicas/imunologia , Vacinas Anticâncer/imunologia , Ensaios Clínicos como Assunto , Glioblastoma/imunologia , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Microambiente Tumoral/imunologia
4.
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
5.
Br J Radiol ; 93(1113): 20200112, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32706978

RESUMO

Interventional oncology (IO) has proven to be highly efficient in the local therapy of numerous malignant tumors in addition to surgery, chemotherapy, and radiotherapy. Due to the advent of immune-oncology with the possibility of tumor control at the molecular and cellular levels, a system change is currently emerging. This will significantly rule oncology in the coming decades. Therefore, one cannot think about IO in the 21st century without considering immunology. For IO, this means paying much more attention to the immunomodulatory effects of the interventional techniques, which have so far been neglected, and to explore the synergistic possibilities with immuno-oncology. It can be expected that the combined use of IO and immuno-oncology will help to overcome the limitations of the latter, such as limited local effects and a high rate of side-effects. To do this, however, sectoral boundaries must be removed and interdisciplinary research efforts must be strengthened. In case of success, IO will face an exciting future.


Assuntos
Imunoterapia/tendências , Oncologia/tendências , Neoplasias/terapia , Vacinas Anticâncer/uso terapêutico , Quimioembolização Terapêutica/métodos , Quimioembolização Terapêutica/tendências , História do Século XXI , Humanos , Imunização Passiva/métodos , Imunomodulação , Imunoterapia/métodos , Imunoterapia Ativa/métodos , Neoplasias/imunologia , Radioterapia (Especialidade)/tendências , Ablação por Radiofrequência/métodos , Ablação por Radiofrequência/tendências , Radioisótopos de Ítrio/uso terapêutico
8.
Urologe A ; 59(7): 797-803, 2020 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-32500171

RESUMO

The first-line therapy of metastatic bladder cancer (urothelial carcinoma, UC) depends on whether a patient is cisplatin-fit or not. Cisplatin-fit patients should be treated with the standard chemotherapy protocol GC (gemcitabine/cisplatin) or alternatively MVAC (methotrexate/vinblastine/doxorubicin/cisplatin). The optimal first-line therapy for cisplatin-unfit patients remains unclear due to the lack of high level of evidence. One criterion for selecting therapy can be the PD-L1 (programmed cell death ligand 1) status of the tumor. The PD-L1-negative patients (PD-L1 <5% for atezolizumab and combined positivity score [CPS] <10 for pembrolizumab) seem to have a greater benefit from the combination chemotherapy GCa (carboplatin/gemcitabine). The PD-L1-positive patients (PD-L1 ≥5% or CPS ≥10) on the other hand may have a greater benefit from and a longer response to the two immune checkpoint inhibitors that are currently approved for this indication, namely atezolizumab and pembrolizumab. Two phase 3 trials that compare head-to-head immunotherapy alone or in combination with chemotherapy vs. chemotherapy alone may help to define the optimal first-line therapy for metastatic UC. Preliminary data from one of these studies indicate an advantage for the combination of immunotherapy with chemotherapy in all subgroups.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Imunoterapia/métodos , Imunoterapia/tendências , Neoplasias Ureterais/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias Urológicas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/imunologia , Carcinoma de Células de Transição/imunologia , Carcinoma de Células de Transição/patologia , Cisplatino/administração & dosagem , Humanos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Resultado do Tratamento , Neoplasias Ureterais/patologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/patologia
10.
Expert Opin Biol Ther ; 20(9): 959-964, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32588674

RESUMO

INTRODUCTION: The COVID-19 pandemic occurred amid the cancer immunotherapy revolution. Immune checkpoint inhibitors (ICIs) have become the standard of care for several solid cancers and are associated with peculiar toxicities, including pneumonitis which has similar features to COVID-19 pneumonia. AREAS COVERED: We summarize the main hallmarks of lung injury induced by ICIs and severe acute respiratory syndrome coronavirus 2 and discuss the critical aspects for differential diagnosis and management. Symptoms and radiological findings are often similar; conversely, treatments are quite different. Furthermore, we focus on potential interactions generating hypotheses that need confirmatory studies. EXPERT OPINION: All cancer patients treated with immunotherapy should receive screening for SARS-CoV-2. This would improve the diagnosis and management of pneumonia and guide therapeutic choices. Furthermore, clinicians could estimate the risk/benefit of continuing ICI treatment in COVID-19 positive patients. Temporary withdrawal of the immunotherapy treatment pending resolution of viral infection may be a reasonable option in long-responders patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Imunoterapia , Neoplasias/terapia , Pneumonia Viral/terapia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Diagnóstico Diferencial , Gerenciamento Clínico , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/tendências , Neoplasias/epidemiologia , Neoplasias/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia
11.
Adv Exp Med Biol ; 1257: 141-154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483737

RESUMO

Natural killer (NK) cells are lymphocytes of the innate immune system that have the ability to recognize malignant cells through balanced recognition of cell-surface indicators of stress and danger. Once activated through such recognition, NK cells release cytokines and induce target cell lysis through multiple mechanisms. NK cells are increasingly recognized for their role in controlling tumor progression and metastasis and as important mediators of immunotherapeutic modalities such as cytokines, antibodies, immunomodulating drugs, and stem cell transplantation. Recent advances in manipulating NK cell number, function, and genetic modification have caused renewed interest in their potential for adoptive immunotherapies, which are actively being tested in clinical trials. Here, we summarize the evidence for NK cell recognition of osteosarcoma, discuss immune therapies that are directly or indirectly dependent on NK cell function, and describe potential approaches for manipulating NK cell number and function to enhance therapy against osteosarcoma.


Assuntos
Neoplasias Ósseas , Células Matadoras Naturais , Osteossarcoma , Neoplasias Ósseas/terapia , Humanos , Imunoterapia/normas , Imunoterapia/tendências , Imunoterapia Adotiva , Osteossarcoma/terapia
12.
Adv Exp Med Biol ; 1257: 155-168, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483738

RESUMO

Interleukin(IL)-12 is a protein that activates T cells and macrophages to kill tumor cells. However, despite this cytokine showing strong antitumor activity in preclinical settings, translation to patients has been slowed by toxic side effects, poor distribution to peripheral tissues, and improper dosing regimens. Osteosarcoma (OS) is an aggressive primary tumor of bone that has shown particular responsiveness to recombinant (r)IL-12 in preclinical models. Poly(lactic-co-glycolic) acid (PLGA) nanospheres, an FDA-approved drug delivery vector, may be a viable delivery vector for transporting biologically active IL-12 to tissues without disturbing normal homeostasis. In this chapter, we explore the potential for using IL-12-loaded nanospheres (IL-12-NS, <1 µm in diameter) to treat cancer, describe the synthesis process, and examine a typical protein release profile while providing insight and future directions of nanoscale tumor immunotherapeutics.


Assuntos
Neoplasias Ósseas , Imunoterapia , Interleucina-12 , Nanocápsulas , Osteossarcoma , Neoplasias Ósseas/terapia , Humanos , Imunoterapia/tendências , Interleucina-12/administração & dosagem , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Osteossarcoma/terapia
13.
Adv Exp Med Biol ; 1257: 169-178, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483739

RESUMO

This chapter discusses a novel target of osteosarcoma (OS), cell-surface vimentin (CSV), and a novel generation of interleukin-12 (IL12), CSV-targeted IL12, for treating OS tumor metastasis. Vimentin is a known intracellular structural protein for mesenchymal cells but is also documented in tumor cells. Our recent study definitively revealed that vimentin can be translocated to the surface of very aggressive tumor cells, such as metastatic cells. This CSV property allows investigators to capture circulating tumor cells (CTCs) across any type of tumor, including OS. CTCs are known as the seeds of metastasis; therefore, targeting these cells using CSV is a logical approach for use in a metastatic OS setting. Interestingly, we found that the peptide VNTANST can bind to CSV when fused to the p40 subunit encoding the DNA of IL12. Systemic delivery of this CSV-targeted IL12 immune therapy inhibited OS metastasis and relapse in a mouse tumor model as detailed in this chapter. This CSV-targeted delivery of IL12 also reduced toxicity of IL12. In summary, this chapter details a novel approach for safe IL12 immune therapy via targeting CSV.


Assuntos
Neoplasias Ósseas , Imunoterapia , Interleucina-12 , Sarcoma , Vimentina , Animais , Neoplasias Ósseas/terapia , Imunoterapia/tendências , Interleucina-12/administração & dosagem , Camundongos , Recidiva Local de Neoplasia , Sarcoma/terapia , Vimentina/metabolismo
14.
Mol Cell ; 78(6): 1019-1033, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32559423

RESUMO

The growing field of immune metabolism has revealed promising indications for metabolic targets to modulate anti-cancer immunity. Combination therapies involving metabolic inhibitors with immune checkpoint blockade (ICB), chemotherapy, radiation, and/or diet now offer new approaches for cancer therapy. However, it remains uncertain how to best utilize these strategies in the context of the complex tumor microenvironment (TME). Oncogene-driven changes in tumor cell metabolism can impact the TME to limit immune responses and present barriers to cancer therapy. These changes also reveal opportunities to reshape the TME by targeting metabolic pathways to favor immunity. Here we explore current strategies that shift immune cell metabolism to pro-inflammatory states in the TME and highlight a need to better replicate physiologic conditions to select targets, clarify mechanisms, and optimize metabolic inhibitors. Unifying our understanding of these pathways and interactions within the heterogenous TME will be instrumental to advance this promising field and enhance immunotherapy.


Assuntos
Imunoterapia/tendências , Neoplasias/metabolismo , Microambiente Tumoral/imunologia , Humanos , Fatores Imunológicos/metabolismo , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/terapia , Microambiente Tumoral/efeitos dos fármacos
16.
Urologe A ; 59(7): 810-816, 2020 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-32468092

RESUMO

BACKGROUND: Great advances have been made for the treatment of urothelial carcinoma by the introduction of checkpoint inhibitors (CPI). Single-agent immunotherapy with CPIs has been approved for patients with metastatic or locally advanced inoperable urothelial carcinoma who have either progressed during or after platinum-based chemotherapy or who are cisplatin-ineligible. For cisplatin-ineligible patients, approval is restricted to patients with high programmed cell death ligand 1 (PD-L1) expression. For patients with nonmuscle invasive bladder cancer (NMIBC) or patients with muscle invasive bladder cancer (MIBC) who receive curative therapy, no CPIs have received approval in Germany. OBJECTIVES: To provide an overview of the current landscape of immunotherapy in patients with urothelial carcinoma. METHODS: Summary of the therapeutic landscape and resulting challenges based on currently published data using a PubMed search. RESULTS: In the treatment of metastatic or inoperable urothelial carcinoma, CPIs represent standard treatment. Depending on the results of currently performed trials, an extension of its use to the perioperative setting (neoadjuvant/adjuvant) and to patients with Bacillus Calmette Guérin (BCG) unresponsive NMIBC in the near future is currently being discussed. CONCLUSIONS: Immuno-oncologic treatment using CPIs has become an integral part of the management of patients with advanced bladder cancer. For biomarker-based patient selection and combination therapies, there is an urgent need for further investigations within clinical trial protocols.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/uso terapêutico , Carcinoma de Células de Transição/terapia , Imunoterapia/tendências , Receptor de Morte Celular Programada 1/uso terapêutico , Neoplasias da Bexiga Urinária/terapia , Neoplasias Urológicas/terapia , Anticorpos Monoclonais , Antígeno B7-H1/metabolismo , Carcinoma de Células de Transição/imunologia , Carcinoma de Células de Transição/patologia , Alemanha , Humanos , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/imunologia , Neoplasias Urológicas/patologia
17.
Urologe A ; 59(7): 804-809, 2020 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-32472222

RESUMO

The approval of the PD­1 and PD-L1 (programmed cell death [ligand] 1) antibodies pembrolizumab, nivolumab, and atezolizumab has fundamentally changed the therapeutic landscape of locally advanced or metastatic urothelial carcinoma. Checkpoint inhibitors (CPI) are the standard of care in second-line treatment if not already used in first line. They replace conventional chemotherapeutics such as vinflunine, paclitaxel, or docetaxel and offer a superior toxicity profile. This article provides an overview of current second-line treatment strategies for locally advanced or metastatic urothelial carcinoma.


Assuntos
Antígeno B7-H1/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Imunoterapia/métodos , Nivolumabe/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias Urológicas/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Humanos , Imunoterapia/tendências , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/patologia
19.
Pediatrics ; 145(5)2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32303583

RESUMO

Peanut allergy is one of the most common food allergies in children, with increasing prevalence over time. The dual-allergen exposure hypothesis now supports transcutaneous sensitization to peanut as a likely pathophysiologic mechanism for peanut allergy development. As a result, there is emerging evidence that early peanut introduction has a role in peanut allergy prevention. Current first-line diagnostic tests for peanut allergy have limited specificity, which may be enhanced with emerging tools such as component-resolved diagnostics. Although management of peanut allergy includes avoidance and carrying an epinephrine autoinjector, risk of fatal anaphylaxis is extremely low, and there is minimal risk related to cutaneous or inhalational exposure. Quality of life in children with peanut allergy requires significant focus. Moving forward, oral and epicutaneous immunotherapy are emerging and exciting tools that may have a role to play in desensitization to peanut.


Assuntos
Arachis/imunologia , Dessensibilização Imunológica/métodos , Hipersensibilidade a Amendoim/imunologia , Hipersensibilidade a Amendoim/terapia , Anafilaxia/imunologia , Anafilaxia/prevenção & controle , Arachis/efeitos adversos , Criança , Dessensibilização Imunológica/tendências , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Hipersensibilidade a Amendoim/diagnóstico , Qualidade de Vida , Literatura de Revisão como Assunto
20.
Nat Med ; 26(4): 475-484, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32273608

RESUMO

Neoadjuvant checkpoint inhibition, in which the therapy is administered before surgery, is a promising new approach to managing bulky but resectable melanoma, and is also being explored in other cancers. This strategy has a high pathologic response rate, which correlates with survival outcomes. The fact that biopsies are routinely available provides a unique opportunity for understanding the responses to therapy and carrying out reverse translation in which these data are used to select therapies in the clinic or in trials that are more likely to improve patient outcomes. In this Perspective, we discuss the rationale for neoadjuvant immunotherapy in resectable solid tumors based on preclinical and human translational data, summarize the results of recent clinical trials and ongoing research, and focus on future directions for enhancing reverse translation.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto/métodos , Terapia Neoadjuvante/métodos , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Ensaios Clínicos como Assunto/estatística & dados numéricos , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Terapia Neoadjuvante/estatística & dados numéricos , Neoplasias/imunologia , Neoplasias/patologia
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