Cord blood-derived cytokine-induced killer cells combined with blinatumomab as a therapeutic strategy for CD19+ tumors.

BACKGROUND: Cytokine-induced killer cells (CIKs) are an advanced therapeutic medicinal product (ATMP) that has shown therapeutic activity in clinical trials but needs optimization. We developed a novel strategy using CIKs from banked cryopreserved cord blood units (CBUs) combined with bispecific antibody (BsAb) blinatumomab to treat CD19+ malignancies. METHODS: CB-CIKs were expanded in vitro and fully characterized in comparison with peripheral blood (PB)-derived CIKs. RESULTS: CB-CIKs, like PB-CIKs, were mostly CD3+ T cells with mean 45% CD3+CD56+ and expressing mostly TCR(T cell receptor)αß with a TH1 phenotype. CB-CIK cultures had, however, a larger proportion of CD4+ cells, mostly CD56-, as well as a greater proportion of naïve CCR7+CD45RA+ and a lower percentage of effector memory cells, compared with PB-CIKs. CB-CIKs were very similar to PB-CIKs in their expression of a large panel of co-stimulatory and inhibitory/exhaustion markers, except for higher CD28 expression among CD8+ cells. Like PB-CIKs, CB-CIKs were highly cytotoxic in vitro against natural killer (NK) cell targets and efficiently lysed CD19+ tumor cells in the presence of blinatumomab, with 30-60% lysis of target cells at very low effector:target ratios. Finally, both CB-CIKs and PB-CIKs, combined with blinatumomab, showed significant therapeutic activity in an aggressive PDX Ph+ CD19+ acute lymphoblastic leukemia model in NOD-SCID mice, without sign of toxicity or graft-versus-host disease. The improved expansion protocol was finally validated in good manufacturing practice conditions, showing reproducible expansion of CIKs from cryopreserved cord blood units with a median of 28.8 × 106 CIK/kg. DISCUSSION: We conclude that CB-CIKs, combined with bispecific T-cell-engaging antibodies, offer a novel, effective treatment strategy for leukemia.

Relação entre ansiedade ao tratamento odontológico e fatores sociodemográficos: estudo com adultos em Santa Catarina (Brasil) / Relationship between anxiety to dentaltreatment and socidemographic factors:a study with adults in Santa Catarina(Brazil)

Introdução: O medo e a ansiedade são emoções preocupantes no consultório odontológico por desencadearem diferentes tipos de comportamento e causarem repercussões somáticas indesejáveis. A reversão do quadro de ansiedade ao tratamento odontológico requer intervenções de diferentes enfoques. Neste sentido, o papel do cirurgião-dentista no processo de redução dos efeitos negativos da ansiedade é essencial. Frente à importância da temática é desejável melhor se conhecer o fenômeno de ansiedade ao tratamento odontológico. Objetivo: identificar a influência de fatores sociodemográficos na determinação de ansiedade ao tratamento odontológico, junto a uma amostra de adultos residentes em Santa Catarina. Métodos: pesquisa descritiva, do tipo transversal, mediante levantamento de dados primários. A população-alvo foi constituída por adultos, residentes em três cidades da região oeste de Santa Catarina (Brasil) e uma cidade do litoral norte catarinense. O plano amostral foi não probabilístico e a obtenção da amostra deu-se por conveniência. A determinação do nível de ansiedade foi efetuada com base numa adaptação da escala de Corah - Dental Anxiety Scale (DAS). Resultados: a amostra constou de 1219 sujeitos, com idades variando de 18 a 87 anos. Os sujeitos classificados entre muito pouco a levemente ansioso (Grupo A - baixo nível) foram os mais frequentes (80 por cento) e 20 por cento eram portadores de moderada a extrema ansiedade (Grupo B - alto nível). A não efetivação de consultas de modo regular foi um pouco mais frequente entre os sujeitos do Grupo B. Conclusão: a maioria do grupo classificado com baixo nível de ansiedade (Grupo A) era de homens, da faixa etária de 50 ou mais anos e com grau de escolaridade superior.

Introduction: Fear and anxiety are disturbing emotions in the dental office for triggering different types of behavior and causing undesirable somatic repercussions. Reversal of anxiety disorders to dental treatment interventions requires different approaches. In this sense, the dentist's role in the reduction process of the negative effects of anxiety is essential. Considering the relevance of the theme it is desirable to understand clearly the anxiety phenomenon to dental treatment. Objective: to identify the influence of socio-demographic factors on the determination of anxiety related to dental treatment, in a sample of adults living in Santa Catarina. Methods: descriptive research, cross-sectional, through primary data collection. The target population consisted of adults living in two cities of the western region and one city of the north coast in Santa Catarina (Brazil). The sampling plan was not probabilistic and obtaining by convenience. To determine the level of anxiety was used an adaptation of Corah Scale - Dental Anxiety Scale (DAS). Results: The sample consisted of 1219 subjects, aged 18-87 years. The subjects rated between very little to look forward slightly (Group A - Low level) were the most common (80 per cent) and 20 per cent suffered from moderate to extreme anxiety (Group B - High level). The non-effective dental appointment was more frequent among subjects with high levels of anxiety (Group B). Conclusion: most in the group rated low anxiety (Group A) were men, older adults (50 or more years) and higher education. In the group with high levels of anxiety (Group B) the majority were women, young adults (18-24 years) and with higher education. The chi-square test revealed a significant association between anxiety and sexy and age.