RESUMEN
Multiple myeloma remains an incurable disease, despite the development of numerous drug classes and combinations that have contributed to improved overall survival. Immunotherapies directed against cancer cell-surface antigens, such as chimeric antigen receptor (CAR) T-cell therapy and T-cell-redirecting bispecific antibodies, have recently received regulatory approvals and shown unprecedented efficacy. However, these immunotherapies have unique mechanisms of action and toxicities that are different to previous treatments for myeloma, so experiences from clinical trials and early access programmes are essential for providing specific recommendations for management of patients, especially as these agents become available across many parts of the world. Here, we provide expert consensus clinical practice guidelines for the use of bispecific antibodies for the treatment of myeloma. The International Myeloma Working Group is also involved in the collection of prospective real-time data of patients treated with such immunotherapies, with the aim of learning continuously and adapting clinical practices to optimise the management of patients receiving immunotherapies.
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Anticuerpos Biespecíficos , Consenso , Mieloma Múltiple , Linfocitos T , Humanos , Anticuerpos Biespecíficos/uso terapéutico , Mieloma Múltiple/inmunología , Mieloma Múltiple/terapia , Mieloma Múltiple/tratamiento farmacológico , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Inmunoterapia/métodos , Inmunoterapia/normas , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversosRESUMEN
Neoadjuvant immunotherapy has achieved exciting efficacy with high clinical complete response (cCR) and pathologic complete response (pCR) rates and durable long-term effects. PD-1 checkpoint blockade-based immunotherapy has been highly successful in microsatellite instability high (MSI-H)/mismatch repair deficiency (dMMR) colorectal cancer and has been recommended as the first-line treatment for metastatic colorectal cancer by domestic and international guidelines. Several studies have shown that immunotherapy can be a potentially curable treatment for MSI-H rectal cancer and has even shown promise in organ preservation in colon cancer. In this study, we first clarified the feasibility of the watch-and-wait strategy after PD-1 checkpoint blockade treatment by indirect and direct evidence. Then from the assessment tools (including digital rectal examination, endoscopy, radiology, and lymph node assessment), the viable assessment methods of cCR for immunotherapy and related difficulties are proposed. Finally, the medication choices of immunotherapy, the treatment regimen, and the follow-up strategy are further discussed. We hope that neoadjuvant immunotherapy could be appropriately applied in MSI-H/dMMR colorectal cancer so that more patients can achieve organ preservation.
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Neoplasias Colorrectales , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Inestabilidad de Microsatélites , Terapia Neoadyuvante , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Inmunoterapia/métodos , Inmunoterapia/normas , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Respuesta Patológica Completa , Espera Vigilante , HumanosRESUMEN
BACKGROUND: The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC. METHOD: Eight paired penile cancer specimens (including penile cancer tissue, paracancerous tissue, and positive lymph node tissue) subjected to whole transcriptome sequencing were analysed to identify differentially expressed genes. We used immunohistochemistry to detect the expression of SPP1 protein and immune cell related proteins in penile cancer tissue. Then, we performed weighted gene coexpression network analysis (WGCNA) to identify the genes related to SPP1 in penile cancer tissue and positive lymph node tissue. Based on the GSE57955 dataset, the CIBERSORT and ssGSEA algorithms were carried out to investigate the immune environment of PSCC. GSVA analysis was conducted to identify the signaling pathways related to SPP1 subgroups. Enzyme-linked immunosorbent assay (ELISA) method was adopted to detect SPP1 level in the serum of 60 patients with penile cancer. RESULTS: Differential analysis indicated that SPP1 was the most differentially upregulated gene in both penile cancer tissues and positive lymph node tissues. Survival analysis suggested that the prognosis of the low-SPP1 group was significantly poorer than that of the high-SPP1 group. Subsequently, immune-related bioinformatics showed that SPP1 was significantly associated with B cells, CD8 + T cells, CD4 + T cells, macrophages, helper T cells, neutrophils and dendritic cells. The immunohistochemical results showed that the high-SPP1 group was characterized by relatively high expression of CD16 and relatively low expression of CD4. GSVA analysis indicated that high-SPP1 group was significantly associated with immune-related pathways such as PD-L1 expression and the PD-1 checkpoint pathway in cancer and the TNF signaling pathway. ELISA demonstrated that the serum level of SPP1 in patients with positive lymph node metastasis of penile cancer was significantly higher than that in patients with negative lymph node metastasis of penile cancer. CONCLUSION: Our study shows that the SPP1 gene might be an effective biomarker for predicting the prognosis and the efficacy of immunotherapy in PSCC patients.
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Carcinoma de Células Escamosas , Osteopontina , Neoplasias del Pene , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Neoplasias del Pene/diagnóstico , Neoplasias del Pene/genética , Neoplasias del Pene/patología , Neoplasias del Pene/terapia , Inmunoterapia/normas , Osteopontina/sangre , Osteopontina/genética , Osteopontina/metabolismo , Biomarcadores de Tumor/sangre , Perfilación de la Expresión Génica , Análisis de Supervivencia , Análisis de Secuencia de ARNRESUMEN
Effective antitumor immunity in mice requires activation of the type I interferon (IFN) response pathway. IFNα and IFNß therapies have proven promising in humans, but suffer from limited efficacy and high toxicity. Intratumoral IFN retention ameliorates systemic toxicity, but given the complexity of IFN signaling, it was unclear whether long-term intratumoral retention of type I IFNs would promote or inhibit antitumor responses. To this end, we compared the efficacy of IFNα and IFNß that exhibit either brief or sustained retention after intratumoral injection in syngeneic mouse tumor models. Significant enhancement in tumor retention, mediated by anchoring these IFNs to coinjected aluminum-hydroxide (alum) particles, greatly improved both their tolerability and efficacy. The improved efficacy of alum-anchored IFNs could be attributed to sustained pleiotropic effects on tumor cells, immune cells, and nonhematopoietic cells. Alum-anchored IFNs achieved high cure rates of B16F10 tumors upon combination with either anti-PD-1 antibody or interleukin-2. Interestingly however, these alternative combination immunotherapies yielded disparate T cell phenotypes and differential resistance to tumor rechallenge, highlighting important distinctions in adaptive memory formation for combinations of type I IFNs with other immunotherapies.
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Hidróxido de Aluminio , Inmunoterapia , Interferón Tipo I , Compuestos de Alumbre/química , Hidróxido de Aluminio/química , Animales , Antineoplásicos/uso terapéutico , Modelos Animales de Enfermedad , Humanos , Inmunoterapia/métodos , Inmunoterapia/normas , Interferón Tipo I/química , Interferón Tipo I/uso terapéutico , Interferón-alfa , Interferón beta , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , RatonesRESUMEN
BACKGROUND: In recent years, the application of functional genetic immuno-oncology screens has showcased the striking ability to identify potential regulators engaged in tumor-immune interactions. Although these screens have yielded substantial data, few studies have attempted to systematically aggregate and analyze them. METHODS: In this study, a comprehensive data collection of tumor immunity-associated functional screens was performed. Large-scale genomic data sets were exploited to conduct integrative analyses. RESULTS: We identified 105 regulator genes that could mediate resistance or sensitivity to immune cell-induced tumor elimination. Further analysis identified MON2 as a novel immune-oncology target with considerable therapeutic potential. In addition, based on the 105 genes, a signature named CTIS (CRISPR screening-based tumor-intrinsic immune score) for predicting response to immune checkpoint blockade (ICB) and several immunomodulatory agents with the potential to augment the efficacy of ICB were also determined. CONCLUSION: Overall, our findings provide insights into immune oncology and open up novel opportunities for improving the efficacy of current immunotherapy agents.
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Sistemas CRISPR-Cas , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Pruebas Genéticas/métodos , Genómica/métodos , Oncología Médica , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Toma de Decisiones Clínicas , Biología Computacional/métodos , Manejo de la Enfermedad , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Inmunoterapia/métodos , Inmunoterapia/normas , Oncología Médica/métodos , Oncología Médica/normas , Pronóstico , Transcriptoma , Resultado del TratamientoAsunto(s)
Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/fisiopatología , Humanos , Inmunoterapia/métodos , Inmunoterapia/normas , Inmunoterapia/tendencias , Neoplasias Hepáticas/fisiopatología , Neoplasias Hepáticas/terapia , Terapia Molecular Dirigida/métodos , Terapia Molecular Dirigida/normas , Terapia Molecular Dirigida/tendenciasRESUMEN
BACKGROUND: The programmed cell death protein - 1 (PD-1) - programmed cell death ligand - 1 (PD-L1) axis is emerging as a promising target for immunotherapy in triple-negative breast cancers (TNBC). AIMS: We analyzed the expression of PD-L1 in TNBC cases, with special emphasis on lymphocyte-predominant tumors along with correlation of the same with clinicopathological features and outcome. SETTINGS AND DESIGN: Tissue microarrays (TMA) were prepared from resection specimens of TNBC cases diagnosed from 2004 to 2008. SUBJECTS AND METHODS: Immunohistochemical staining was performed on the TMA using the ventana PD-L1 antibody (Clone SP 263). STATISTICAL ANALYSIS: Chi-square test was used for correlation of PD-L1 positivity in tumor and immune cells with clinicopathological features. Univariate and multivariate survival analyses were carried out using the Kaplan Meir and Cox Regression methods, respectively. RESULTS: Overall, PD-L1 staining was seen in 35.9% (66 out of 184) tumors. PD-L1 positivity of tumor cells was seen in 14.7% (27 out of 184 cases), whereas stromal immune cell expression was observed in 21.2% (39 out of 184) cases. Lymphocyte-predominant tumors showed statistically significant expression of PD-L1 in both tumor (P < 0.0001) and immune cells (P 0.036). On univariate analysis, PD-L1 in immune cells was associated with good overall survival (P 0.05) as well as disease-free survival (P 0.013). On multivariate analysis, the same was associated with a significantly decreased risk for recurrence (P 0.018). CONCLUSION: PD-L1 expression in stromal immune cells proved to be a significant prognostic factor for TNBC. This data can serve as a baseline to plan clinical trials with anti-PD-L1 drugs for TNBC in the Indian setting.
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Apoptosis/efectos de los fármacos , Antígeno B7-H1/uso terapéutico , Carcinoma/tratamiento farmacológico , Inmunoterapia/estadística & datos numéricos , Inmunoterapia/normas , Ligandos , Neoplasias de la Mama Triple Negativas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND & AIMS: Intratumor molecular heterogeneity is a key feature of tumorigenesis and is linked to treatment failure and patient prognosis. Herein, we aimed to determine what drives tumor cell evolution by performing single-cell transcriptomic analysis. METHODS: We analyzed 46 hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) biopsies from 37 patients enrolled in interventional studies at the NIH Clinical Center, with 16 biopsies collected before and after treatment from 7 patients. We developed a novel machine learning-based consensus clustering approach to track cellular states of 57,000 malignant and non-malignant cells including tumor cell transcriptome-based functional clonality analysis. We determined tumor cell relationships using RNA velocity and reverse graph embedding. We also studied longitudinal samples from 4 patients to determine tumor cellular state and its evolution. We validated our findings in bulk transcriptomic data from 488 patients with HCC and 277 patients with iCCA. RESULTS: Using transcriptomic clusters as a surrogate for functional clonality, we observed an increase in tumor cell state heterogeneity which was tightly linked to patient prognosis. Furthermore, increased functional clonality was accompanied by a polarized immune cell landscape which included an increase in pre-exhausted T cells. We found that SPP1 expression was tightly associated with tumor cell evolution and microenvironmental reprogramming. Finally, we developed a user-friendly online interface as a knowledge base for a single-cell atlas of liver cancer. CONCLUSIONS: Our study offers insight into the collective behavior of tumor cell communities in liver cancer as well as potential drivers of tumor evolution in response to therapy. LAY SUMMARY: Intratumor molecular heterogeneity is a key feature of tumorigenesis that is linked to treatment failure and patient prognosis. In this study, we present a single-cell atlas of liver tumors from patients treated with immunotherapy and describe intratumoral cell states and their hierarchical relationship. We suggest osteopontin, encoded by the gene SPP1, as a candidate regulator of tumor evolution in response to treatment.
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Carcinoma Hepatocelular/tratamiento farmacológico , Inmunoterapia/normas , Células Neoplásicas Circulantes/efectos de los fármacos , Células Neoplásicas Circulantes/ultraestructura , Biopsia/métodos , Biopsia/estadística & datos numéricos , Carcinoma Hepatocelular/fisiopatología , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/fisiopatología , Humanos , Inmunoterapia/métodos , Inmunoterapia/estadística & datos numéricos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Células Neoplásicas Circulantes/clasificaciónRESUMEN
Non-AIDS-defining cancers are a growing source of morbidity for people with HIV globally. Although people living with HIV have a disproportionately increased risk of developing virally mediated cancers, cancer burden for common non-AIDS-defining cancers that are not virally associated and are linked to ageing, such as prostate cancer, is becoming higher than for virally mediated cancers. Ageing, behavioural, and HIV-specific factors drive the incidence and affect the outcomes of non-AIDS-defining cancers, presenting different challenges for addressing global morbidity and mortality from non-AIDS-defining cancer. Although large population-based studies have shown that people living with HIV with non-AIDS-defining cancers have poorer cancer outcomes than do people without HIV, current guidelines emphasise that people living with HIV with non-AIDS-defining cancers should receive standard, guideline-based treatment, and infectious disease and oncology providers should work closely to address potential drug interactions between antiretroviral therapy and antineoplastic treatment. Most trials target preventive measures focusing on non-AIDS-defining cancers. However, treatment trials for the optimal management of people living with HIV and non-AIDS-defining cancer, including interventions such as immunotherapies, are needed to improve non-AIDS-defining cancer outcomes.
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Síndrome de Inmunodeficiencia Adquirida/terapia , Infecciones por VIH/terapia , Neoplasias/terapia , Sarcoma de Kaposi/terapia , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Terapia Antirretroviral Altamente Activa , VIH/patogenicidad , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Humanos , Inmunoterapia/normas , Neoplasias/epidemiología , Neoplasias/etiología , Factores de Riesgo , Sarcoma de Kaposi/epidemiología , Sarcoma de Kaposi/etiología , Sarcoma de Kaposi/patología , Resultado del TratamientoRESUMEN
Cancer immunotherapy based on the use of antibodies targeting the so-called checkpoint inhibitors, such as programmed cell death-1 receptor, its ligand, or CTLA-4, has shown durable clinical benefit and survival improvement in melanoma and other tumors. However, there are some special situations that could be a challenge for clinical management. Persons with chronic infections, such as HIV-1 or viral hepatitis, latent tuberculosis, or a history of solid organ transplantation, could be candidates for cancer immunotherapy, but their management requires a multidisciplinary approach. The Spanish Melanoma Group (GEM) panel in collaboration with experts in virology and immunology from different centers in Spain reviewed the literature and developed evidence-based guidelines for cancer immunotherapy management in patients with chronic infections and immunosuppression. These are the first clinical guidelines for cancer immunotherapy treatment in special challenging populations. Cancer immunotherapy in chronically infected or immunosuppressed patients is feasible but needs a multidisciplinary approach in order to decrease the risk of complications related to the coexistent comorbidities.
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Enfermedades Transmisibles/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Huésped Inmunocomprometido , Inmunoterapia/normas , Oncología Médica/normas , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/terapia , Comorbilidad , Consenso , Medicina Basada en la Evidencia , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Melanoma/epidemiología , Melanoma/inmunología , Medición de Riesgo , Factores de Riesgo , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/inmunología , Resultado del TratamientoRESUMEN
INTRODUCTION: Pembrolizumab, a monoclonal antibody targeting programmed cell death-1 (PD-1), is approved as a therapy for unresectable or metastatic melanoma. Immunotherapy-associated pneumonitis is an uncommon event. PATIENT CONCERNS: A 73-year-old man was admitted to our hospital with a history of melanoma on the left side of the face (resected in December 2012) and metastasis to the left lung upper lobe (resected in November 2016). Recurrence of metastasis to the bilateral lungs and left pleura was detected in April 2018. A complete response was achieved following treatment with pembrolizumab, with lower limb rashes the only adverse events occurring during therapy. The patient was readmitted in March 2019 with a productive cough, shortness of breath, and mild fever, and sputum culture identified Escherichia coli. DIAGNOSIS: A diagnosis of pneumonia was made, and although cough and shortness of breath responded to ceftazidime and levofloxacin, but fever and poor appetite persisted. Computed tomography showed no improvement in the bilateral lower lobe lesions. Prednisone was initiated based on a clinical diagnosis of immunotherapy-related pneumonitis. The response to prednisone confirmed the diagnosis. INTERVENTIONS: The patient first received ceftazidime and levofloxacin, but the symptoms persisted. Prednisone was initiated based on a clinical diagnosis of immunotherapy-related pneumonitis. OUTCOME: Complete resolution of the bilateral lung lesions occurred after 45 days of prednisone therapy. CONCLUSION: This case report highlights that both pneumonitis and bacterial pneumonia can occur as complications of anti-PD-1 immunotherapy.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Inmunoterapia/efectos adversos , Melanoma/tratamiento farmacológico , Neumonía Bacteriana/etiología , Neumonía/etiología , Anciano , Tos/etiología , Disnea/etiología , Fiebre/etiología , Humanos , Inmunoterapia/métodos , Inmunoterapia/normas , Masculino , Melanoma/complicaciones , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/fisiopatología , Neumonía/fisiopatología , Neumonía Bacteriana/fisiopatologíaAsunto(s)
COVID-19/prevención & control , Dermatología/normas , Medicina Basada en la Evidencia/normas , Inmunoterapia/normas , Enfermedades de la Piel/tratamiento farmacológico , Productos Biológicos/administración & dosificación , Productos Biológicos/efectos adversos , COVID-19/diagnóstico , COVID-19/inmunología , COVID-19/virología , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/efectos adversos , Inmunoterapia/efectos adversos , Guías de Práctica Clínica como Asunto , SARS-CoV-2/inmunología , Índice de Severidad de la Enfermedad , Enfermedades de la Piel/inmunologíaRESUMEN
ABSTRACT: The present study aimed to evaluate the role of early F-18 2-deoxy-2-[fluorine-18] fluoro-D-glucose positron emission tomography/computed tomography (FDG PET/CT) in non-small cell lung cancer patients undergoing immune checkpoint inhibitor (ICI) treatment.Twenty-four non-small cell lung cancer patients who received nivolumab or pembrolizumab and underwent FDG PET/CT as an interim analysis after 2 or 3 cycles of ICI treatment were retrospectively enrolled. Tumor response was assessed using the PET Response Criteria in Solid Tumors 1.0 (PERCIST) and the European Organization for Research and Treatment of Cancer (EORTC) criteria after 2 or 3 cycles of ICI treatment (SCAN-1) and after an additional 2 cycles of ICI treatment (SCAN-2). The best overall response was determined by FDG PET/CT or chest CT at ≥ 3 months after therapy initiation, and the clinical benefit was investigated. progression-free survival was investigated, and its correlation with clinicopathologic and metabolic parameters was examined using a Cox multivariate proportional hazards model.In the interim analysis, 4 patients achieved a complete metabolic response (CMR), 1 patient exhibited a partial metabolic response (PMR), and 14 patients had Progressive metabolic disease (PMD) according to the PERCIST and EORTC criteria. Four patients showed stable metabolic disease (SMD) according to the PERCIST criteria, and 2 patients showed different responses (i.e., PMR) according to the EORTC criteria. Patients with a CMR or PMR at SCAN-1 had a clinical benefit. Among the 4 patients with SMD at SCAN-1, only 1 experienced a clinical benefit regardless of the percent change in the peak standardized uptake value. Two patients with discordant response assessments between the PERCIST and EORTC criteria showed conflicting clinical benefits. Among the 14 patients with PMD, none experienced any clinical benefit. Only metabolic parameters were significant factors for predicting progression in the multivariate analysis (peak standardized uptake value and metabolic tumor volume, HRs of 1.18 and 1.00, respectively).Based on early F-18 FDG PET/CT after ICI treatment, metabolic parameters could predict post-treatment progression. Responses after ICI treatment were correctly assessed in patients with a CMR, a PMR, and PMD, but patients with SMD required a meticulous follow-up because of varying clinical benefits.
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Carcinoma de Pulmón de Células no Pequeñas/terapia , Inmunoterapia/normas , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Femenino , Humanos , Inmunoterapia/métodos , Masculino , Persona de Mediana Edad , Nivolumab/uso terapéutico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: The spread of misinformation has accompanied the coronavirus pandemic, including topics such as immune boosting to prevent COVID-19. This study explores how immune boosting is portrayed on the internet during the COVID-19 pandemic. DESIGN: Content analysis. METHODS: We compiled a dataset of 227 webpages from Google searches in Canada and the USA using the phrase 'boost immunity' AND 'coronavirus' on 1 April 2020. We coded webpages for typology and portrayal of immune boosting and supplements. We recorded mentions of microbiome, whether the webpage was selling or advertising an immune boosting product or service, and suggested strategies for boosting immunity. RESULTS: No significant differences were found between webpages that appeared in the searches in Canada and the USA. The most common types of webpages were from news (40.5%) and commercial (24.7%) websites. The concept of immune boosting was portrayed as beneficial for avoiding COVID-19 in 85.5% of webpages and supplements were portrayed as beneficial in 40% of the webpages, but commercial sites were more likely to have these portrayals. The top immune boosting strategies were vitamin C (34.8%), diet (34.4%), sleep (34.4%), exercise (30.8%) and zinc (26.9%). Less than 10% of the webpages provide any critique of the concept of immune boosting. CONCLUSIONS: Pairing evidence-based advice for maintaining one's health (eg, healthy diet, exercise, sleep) with the phrase immune boosting and strategies lacking in evidence may inadvertently help to legitimise the concept, making it a powerful marketing tool. Results demonstrate how the spread of misinformation is complex and often more subtle than blatant fraudulent claims.
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Comunicación , Información de Salud al Consumidor , Infecciones por Coronavirus , Factores Inmunológicos , Inmunoterapia , Internet , Mercadotecnía , Pandemias , Neumonía Viral , Betacoronavirus , COVID-19 , Canadá/epidemiología , Información de Salud al Consumidor/métodos , Información de Salud al Consumidor/normas , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Exactitud de los Datos , Suplementos Dietéticos/normas , Humanos , Factores Inmunológicos/normas , Factores Inmunológicos/uso terapéutico , Inmunoterapia/métodos , Inmunoterapia/normas , Difusión de la Información/ética , Difusión de la Información/métodos , Internet/estadística & datos numéricos , Internet/tendencias , Mercadotecnía/ética , Mercadotecnía/métodos , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Neumonía Viral/prevención & control , Salud Pública , SARS-CoV-2 , Estados Unidos/epidemiologíaRESUMEN
Immunotherapy is a very promising therapeutic approach against cancer that is particularly effective when combined with gene therapy. Immuno-gene therapy approaches have led to the approval of four advanced therapy medicinal products (ATMPs) for the treatment of p53-deficient tumors (Gendicine and Imlygic), refractory acute lymphoblastic leukemia (Kymriah) and large B-cell lymphomas (Yescarta). In spite of these remarkable successes, immunotherapy is still associated with severe side effects for CD19+ malignancies and is inefficient for solid tumors. Controlling transgene expression through an externally administered inductor is envisioned as a potent strategy to improve safety and efficacy of immunotherapy. The aim is to develop smart immunogene therapy-based-ATMPs, which can be controlled by the addition of innocuous drugs or agents, allowing the clinicians to manage the intensity and durability of the therapy. In the present manuscript, we will review the different inducible, versatile and externally controlled gene delivery systems that have been developed and their applications to the field of immunotherapy. We will highlight the advantages and disadvantages of each system and their potential applications in clinics.
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Terapia Genética , Inmunoterapia , Animales , Biomarcadores , Regulación de la Expresión Génica , Terapia Genética/métodos , Terapia Genética/normas , Humanos , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Inmunoterapia/normas , Terapia Molecular Dirigida , Transgenes , Investigación Biomédica TraslacionalRESUMEN
Talimogene laherparepvec (T-VEC) is the first agent approved for cancer in the emerging class of oncolytic viral therapies. While T-VEC was approved for the treatment of advanced melanoma in 2015, clinical utilization has been hampered by rapid changes in the therapeutic landscape of melanoma related to advances in both immune checkpoint blockade and targeted therapy, cumbersome logistics involved in T-VEC administration, biosafety concerns, and a perception that T-VEC has limited impact on uninjected, visceral disease. However, with further survival follow-up from the phase III OPTiM (OncovexGM-CSF Pivotal Trial in Melanoma), along with new real-world data and consensus guidelines on safe administration of oncolytic viruses, a roadmap for when and how to use T-VEC has been emerging. In addition, preliminary data have demonstrated improved therapeutic responses to T-VEC in combination with immune checkpoint blockade in patients with melanoma without additive toxicity. This review provides an update on recent data with T-VEC alone and in combination with other agents. The emerging data provide guidance for how to better utilize T-VEC for patients with melanoma and identifies critical areas for clinical investigation to expand the role of T-VEC in combination strategies for the treatment of melanoma and perhaps other cancers.
Asunto(s)
Productos Biológicos/administración & dosificación , Inmunoterapia/normas , Melanoma/terapia , Guías de Práctica Clínica como Asunto , Neoplasias Cutáneas/terapia , Productos Biológicos/efectos adversos , Ensayos Clínicos Fase III como Asunto , Contención de Riesgos Biológicos/normas , Herpesvirus Humano 1 , Humanos , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Inmunoterapia/tendencias , Inyecciones Intralesiones , Melanoma/diagnóstico , Melanoma/inmunología , Melanoma/mortalidad , Viroterapia Oncolítica/métodos , Viroterapia Oncolítica/normas , Viroterapia Oncolítica/tendencias , Virus Oncolíticos/inmunología , Virus Oncolíticos/patogenicidad , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Background: Oral immunotherapy for cow's milk allergy is an effective treatment option because of its ability to increase the threshold for clinical reactions. Aims: To present our experience of oral immunotherapy for cow's milk allergy in the pediatric allergy outpatient clinic, and to evaluate the long-term efficacy of oral immunotherapy and risk factors for adverse reactions during oral immunotherapy. Study Design: Single-center retrospective cohort study. Methods: Forty-two patients with Immunoglobulin-E-mediated cow's milk allergy who complied with the oral immunotherapy protocol were evaluated in this study. The treatment consisted of a rapid escalation phase with an oral food challenge step that included milk doses. During the build-up phase, increasing quantities of cow's milk were administered until the patient was able to consume 200 mL of cow's milk daily. Results: The mean age of starting the oral immunotherapy was 40.2±3.2 (range, 36-156) months, and 54.8% (n=23) of the patients were males. The mean duration of the build-up phase was 18.1±5.6 (range, 9-41) weeks, and the mean maintenance phase was 29.1±11.6 (range, 12-63) months. During the oral immunotherapy, 36 adverse reactions (78% mild and 22% moderate) occurred in 16 (38%) patients. There were no differences in the age of starting the oral immunotherapy (p=0.19), cow's milk-specific Immunoglobulin-E levels (p=0.17), and cumulative provocative doses of oral food challenges (p=0.78) between the two groups of patients with and without adverse reactions. The wheal diameters to cow's milk were higher in the group with adverse reactions (p=0.03). There was no difference in the oral immunotherapy onset age between patients with and without a history of anaphylaxis (p=0.38). The patients with a history of anaphylaxis had more adverse reactions (p=0.04) and a higher number of reactions during the oral immunotherapy (p=0.01), and a higher mean duration of the up-dosing phase (p=0.04) compared with patients without anaphylaxis. Conclusion: Oral immunotherapy is a treatment option in patients with cow's milk allergy because of its high efficacy. Adverse reactions occur in about 40% of cases and are mostly mild. It should be administered with caution to patients with a history of anaphylaxis and a higher wheal diameter to cow's milk in the skin prick test.
Asunto(s)
Inmunoterapia/normas , Hipersensibilidad a la Leche/tratamiento farmacológico , Administración Oral , Adolescente , Animales , Bovinos , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Inmunoterapia/métodos , Inmunoterapia/estadística & datos numéricos , Masculino , Leche/efectos adversos , Leche/inmunología , Hipersensibilidad a la Leche/inmunología , Estudios Retrospectivos , Pruebas Cutáneas/métodos , Resultado del Tratamiento , TurquíaRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic is concerning for patients with neuroimmunological diseases who are receiving immunotherapy. Uncertainty remains about whether immunotherapies increase the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or increase the risk of severe disease and death upon infection. National and international societies have developed guidelines and statements, but consensus does not exist in several areas. In this Review, we attempt to clarify where consensus exists and where uncertainty remains to inform management approaches based on the first principles of neuroimmunology. We identified key questions that have been addressed in the literature and collated the recommendations to generate a consensus calculation in a Delphi-like approach to summarize the information. We summarize the international recommendations, discuss them in light of the first available data from patients with COVID-19 receiving immunotherapy and provide an overview of management approaches in the COVID-19 era. We stress the principles of medicine in general and neuroimmunology in particular because, although the risk of viral infection has become more relevant, most of the considerations apply to the general management of neurological immunotherapy. We also give special consideration to immunosuppressive treatment and cell-depleting therapies that might increase susceptibility to SARS-CoV-2 infection but reduce the risk of severe COVID-19.