Immunotherapy for neuroblastoma using syngeneic fibroblasts transfected with IL-2 and IL-12

Cytokine-modified tumour cells have been used in clinical trials for immunotherapy of neuroblastoma, but primary tumour cells from surgical biopsies are difficult to culture. Autologous fibroblasts, however, are straightforward to manipulate in culture and easy to transfect using nonviral or viral vectors. Here we have compared the antitumour effect of fibroblasts and tumour cells transfected ex vivo to coexpress interleukin-2 (IL-2) and IL-12 in a syngeneic mouse model of neuroblastoma. Coinjection of cytokine-modified fibroblasts with Neuro-2A tumour cells abolished their in vivo tumorigenicity. Treatment of established tumours with three intratumoral doses of transfected fibroblasts showed a significant therapeutic effect with reduced growth or complete eradication of tumours in 90% of mice, associated with extensive leukocyte infiltration. Splenocytes recovered from vaccinated mice showed enhanced IL-2 production following Neuro-2A coculture, and increased cytotoxicity against Neuro-2A targets compared with controls. Furthermore, 100% of the tumour-free mice exhibited immune memory against tumour cells when rechallenged three months later. The potency of transfected fibroblasts was equivalent to that of tumour cells in all experiments. We conclude that syngeneic fibroblasts cotransfected with IL-2 and IL-12 mediate therapeutic effects against established disease, and are capable of generating immunological memory. Furthermore, as they are easier to recover and manipulate than autologous tumour cells, fibroblasts provide an attractive alternative immunotherapeutic strategy for the treatment of neuroblastoma

Maternal Autonomy and Attitudes Towards Gender Norms: Associations with Childhood Immunization in Nigeria

OBJECTIVES: Globally 2.5 million children under-five die from vaccine preventable diseases, and in Nigeria only 23% of children ages 12–23 months are fully immunized. The international community is promoting gender equality as a means to improve the health and well-being of women and their children. This paper looks at whether measures of gender equality, autonomy and individual attitudes towards gender norms, are associated with a child being fully immunized in Nigeria. METHODS: Data from currently married women with a child 12–23 months from the 2008 Nigeria Demographic and Health Survey (DHS) were used to study the influence of autonomy and gender attitudes on whether or not a child is fully immunized. Multivariate logistic regression was used and several key socioeconomic variables were controlled for including wealth and education, which are considered key inputs into gender equality. RESULTS: Findings indicated that household decision-making and attitudes towards wife beating were significantly associated with a child being fully immunized after controlling for socioeconomic variables. Ethnicity, wealth and education were also significant factors. CONCLUSIONS: Programmatic and policy implications indicate the potential for the promotion of gender equality as a means to improve child health. Gender equality can be seen as a means to enable women to access life-saving services for their children