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1.
Cell ; 183(1): 4-10, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32979319

RESUMEN

The SARS-CoV-2 pandemic has posed a significant challenge for risk evaluation and mitigation among cancer patients. Susceptibility to and severity of COVID-19 in cancer patients has not been studied in a prospective and broadly applicable manner. CAPTURE is a pan-cancer, longitudinal immune profiling study designed to address this knowledge gap.


Asunto(s)
Infecciones por Coronavirus/complicaciones , Monitorización Inmunológica/métodos , Neoplasias/complicaciones , Neumonía Viral/complicaciones , Anticuerpos Antivirales/inmunología , COVID-19 , Infecciones por Coronavirus/inmunología , Humanos , Estudios Longitudinales , Neoplasias/inmunología , Neoplasias/virología , Pandemias , Neumonía Viral/inmunología
2.
Nat Cancer ; 2: 1321-1337, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34950880

RESUMEN

CAPTURE (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable neutralizing antibody titers (NAbT) against SARS-CoV-2 variants of concern (VOCs) vs wildtype (WT). Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT vs solid cancers against both WT and VOCs. In comparison with individuals without cancer, patients with haematological, but not solid, malignancies had reduced NAb responses. Seroconversion showed poor concordance with NAbT against VOCs. Prior SARS-CoV-2 infection boosted NAb response including against VOCs, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T-cell responses were detected in 80% of patients, and were comparable between vaccines or cancer types. Our results have implications for the management of cancer patients during the ongoing COVID-19 pandemic.


Asunto(s)
Inmunidad Adaptativa/inmunología , Anticuerpos Neutralizantes/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/inmunología , Carcinoma de Células Renales/complicaciones , Neoplasias Renales/complicaciones , SARS-CoV-2/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Vacuna BNT162/administración & dosificación , Vacuna BNT162/inmunología , COVID-19/complicaciones , COVID-19/epidemiología , Vacunas contra la COVID-19/administración & dosificación , ChAdOx1 nCoV-19/administración & dosificación , ChAdOx1 nCoV-19/inmunología , Femenino , Humanos , Inmunogenicidad Vacunal/inmunología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Estudios Prospectivos , SARS-CoV-2/genética , SARS-CoV-2/fisiología , Linfocitos T/inmunología , Linfocitos T/virología , Vacunación/métodos
3.
Res Sq ; 2021 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-34580668

RESUMEN

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer.

4.
Nat Cancer ; 2(12): 1321-1337, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-35121900

RESUMEN

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/inmunología , Neoplasias/complicaciones , Linfocitos T/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/sangre , COVID-19/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Inmunidad Celular , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/inmunología , Estudios Prospectivos , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto Joven
5.
Nat Cancer ; 2(12): 1305-1320, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-35121899

RESUMEN

Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) ( NCT03226886 ) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic.


Asunto(s)
Vacuna BNT162/inmunología , COVID-19/prevención & control , ChAdOx1 nCoV-19/inmunología , Neoplasias/inmunología , SARS-CoV-2/inmunología , Anciano , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacuna BNT162/administración & dosificación , COVID-19/sangre , COVID-19/inmunología , ChAdOx1 nCoV-19/administración & dosificación , Femenino , Humanos , Inmunidad Celular , Inmunogenicidad Vacunal , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/complicaciones , Estudios Prospectivos , Linfocitos T/inmunología
6.
Expert Opin Investig Drugs ; 29(7): 739-753, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32401070

RESUMEN

Introduction: Advanced melanoma historically had a very poor outcome but targeted therapies and immune checkpoint inhibitors (IC) have changed the course of the disease and made durable responses possible. However, most patients will develop progressive disease, so further strategies to overcome treatment resistance are needed. Areas covered: Current treatment strategies and landmark trials are discussed. Novel targeted agents, immune checkpoint inhibitors, and further immune-modulatory drugs, cancer vaccines and tumor infiltrating lymphocytes and their potential role in the treatment of melanoma are described. Current trials investigating these emerging agents and treatment strategies were searched for on ClinicalTrials.gov and are presented on the background of the current literature explaining the rationale for employing these new agents and strategies. Combinations of tumor-directed agents with those causing immune augmentation as well as a new adjuvant and neoadjuvant strategies are discussed. Expert opinion: Questions regarding treatment combination, personalization, and sequence of treatment will become increasingly important and will be guided by new biomarkers. New treatment settings will broaden the patient selection and will highlight the need for further discussions regarding toxicity in long-term survivorship.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Melanoma/tratamiento farmacológico , Terapia Molecular Dirigida , Animales , Biomarcadores de Tumor/metabolismo , Vacunas contra el Cáncer/administración & dosificación , Desarrollo de Medicamentos , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inmunoterapia/métodos , Melanoma/inmunología , Melanoma/patología , Metástasis de la Neoplasia , Selección de Paciente
7.
Expert Rev Anticancer Ther ; 20(5): 343-354, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32293937

RESUMEN

Introduction: The incidence of advanced renal cell carcinoma (RCC) is increasing. Over the last 10 years targeted therapies have led to improved efficacy outcomes for renal carcinoma, including longer survival. However, the majority of patients develop disease progression within a year of initiation of first-line therapy. Recently a number of new regimens have been investigated including the combination of immune checkpoint inhibitors with VEGF inhibitors.Areas covered: In this review, we assess the efficacy and safety of avelumab/axitinib in treatment-naïve patients with metastatic RCC and compare this combination to other current and emerging treatment regimens. In the Javelin 101 phase III registration trial, avelumab/axitinib demonstrated superior response rates and progression-free survival compared to sunitinib. However, after follow-up of 11.6 months, there was no significant difference in overall survival (OS). Avelumab/axitinib showed a tolerable safety profile. Adverse events were manageable and were in line with expected toxicities from the single agents.Expert Opinion: Avelumab/axitinib has shown impressive efficacy and a tolerable safety profile in metastatic RCC. The future role of this treatment combination in the rapidly evolving landscape of novel combinations in this disease will have to be defined.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Axitinib/administración & dosificación , Carcinoma de Células Renales/patología , Progresión de la Enfermedad , Humanos , Neoplasias Renales/patología , Supervivencia sin Progresión , Tasa de Supervivencia , Resultado del Tratamiento
8.
Virchows Arch ; 467(5): 543-50, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26384025

RESUMEN

Neuroendocrine tumors (NET) are routinely graded and staged to judge prognosis. Proliferation index using MIB1 staining has been introduced to assess grading. There are vivid discussions on cutoff definitions, automated counting, and interobserver variability. However, no data exist regarding interlaboratory reproducibility for low proliferation indices which are of importance to discriminate between G1 and G2 NET. We performed MIB1 staining in three different university hospital-based pathology laboratories on a tissue micro array (TMA) of a well-characterized patient cohort, containing pancreatic NET of 61 patients. To calculate the proliferation index, number of positive tumor nuclei was divided by the total number of tumor nuclei. Labeling index was compared to mitotic counts in whole tissue sections and to clinical outcome. Linear regression analysis, intraclass comparison, and log-rank analysis were performed. Intraclass correlation showed moderate-to-fair agreement. Especially low proliferating tumors were affected by interlaboratory differences. Log-rank analysis was performed for each lab and resulted in three different cutoffs (5.0, 3.0, and 0.5 %). Every calculated cutoff stratified the patient cohort to a significant extent for the underlying stain (p < 0.001, <0.001, and <0.001) but showed no or lesser significance when applied to the other stains. Significant and relevant interlab differences for MIB1 exist. Since the MIB1 proliferation index influences grading, local cutoffs or external standardization should urgently be introduced to achieve reliability and reproducibility.


Asunto(s)
Tumores Neuroendocrinos/diagnóstico , Neoplasias Pancreáticas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice Mitótico/métodos , Clasificación del Tumor/métodos , Variaciones Dependientes del Observador , Pronóstico , Reproducibilidad de los Resultados , Coloración y Etiquetado , Adulto Joven
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