RESUMO
BACKGROUND: BTH1677 is a beta-glucan pathogen-associated molecular pattern (PAMP) being evaluated as a novel immunotherapy of cancer. We previously described that the presence of antibodies against beta-glucan (ABA) in serum is necessary for BTH1677 antitumoral activity. We hypothesized that infusion of immunoglobulin can reinstate responses to BTH1677 in individuals with low ABA levels. PATIENTS AND METHODS: We report two single-patient studies: one in a patient with metastatic colorectal cancer who received BTH1677, combined with tumor targeting antibody cetuximab; and a second in a patient with metastatic neuroendocrine tumor who received BTH1677 combined with immune checkpoint inhibitor pembrolizumab. RESULTS: The patients had low serum titers of ABA and low innate immune effector functionality induced by BTH1677. Addition of intravenous immunoglobulins restored innate immune activity of BTH1677 and induced clinically meaningful anti-tumoral activity, with long-term disease control. CONCLUSION: Infusion of immunoglobulin can restore activity of BTH1677 in individuals with low serum ABA level.
Assuntos
Anticorpos/sangue , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Glucanos/administração & dosagem , Tumores Neuroendócrinos/imunologia , Tumores Neuroendócrinos/terapia , beta-Glucanas/imunologia , Idoso de 80 Anos ou mais , Anticorpos/imunologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Cetuximab/administração & dosagem , Feminino , Humanos , Imunoglobulinas/administração & dosagem , Imunoterapia/métodos , Pessoa de Meia-IdadeRESUMO
The degree of certainty in epidemiological studies is probably limited more by estimates of exposure than by any other component. We present a methodology for computing daily pollutant concentration fields that reduces exposure uncertainty and bias by taking account of spatial variation in air quality. This approach, using elliptical influence functions, involves the optimum blending of observations from a monitoring network with gridded pollution fields predicted by the complex air quality model TAPM. Such fields allow more information to be incorporated in the exposure fields used in epidemiological studies, rather than having to assume that ambient exposure is the same across a whole city and/or that individuals remain at the one location for the duration of a study.