Recommandations: Nous avons formule 15 recommandations concernant le depistage et d'autres soins preventifs et 1 recommandation de nature politique visant a ameliorer l'acces aux soins primaires. ...Ainsi, nous recommandons de prioriser une strategie de communication pour le depistage du cancer colorectal a partir de l'age de 45 ans et pour l'evaluation du risque de maladie cardiovasculaire pour lutter contre les iniquites en matiere de sante et promouvoir la sante. Les interventions particulieres qui devraient etre deployees pour lutter contre les iniquites comprennent l'autodepistage du virus du papillome humain (VPH) et du VIH, et le test de liberation de l'interferon y pour l'infection tuberculeuse. Le depistage de la depression, de la toxicomanie, de la violence conjugale et de la pauvrete devrait egalement permettre aux personnes touchees d'acceder plus facilement a des interventions eprouvees. Nous recommandons une prise de contact systematique avec des professionnels de la sante en soins primaires pour les personnes defavorisees.
Purpose IFN4N is a glycoengineered version of recombinant human interferon alpha 2 (rhIFN-alpha2) that was modified to exhibit four N-glycosylation sites. It shows reduced in vitro specific ...biological activity (SBA) mainly due to R23 mutation by N23. However, it has improved pharmacokinetics and led to a high in vivo antitumor activity in mice. In order to prepare a new IFN-based biobetter, this work compares the influence of glycosylation (affecting pharmacokinetics) with the in vitro antiproliferative SBA on the in vivo efficacy. Methods Based on IFN4N, three groups of muteins were designed, produced, and characterized. Group A: variants with the same glycosylation degree (4N) but higher in vitro antiproliferative SBA (R23 restored); group B: muteins with higher glycosylation degree (5N) but similar in vitro antiproliferative activity; and group C: variants with improved glycosylation (5N and 6N) and in vitro antiproliferative bioactivity. Results Glycoengineering was successful for improving pharmacokinetics, and R23 restoration considerably increased in vitro antiproliferative activity of new muteins compared to IFN4N. Hyperglycosylation was able to improve the in vivo efficacy similarly to or even better than R23 restoration. Additionally, the highest glycosylated mutein exhibited the lowest immunogenicity. Conclusions Hyperglycosylation constitutes a successful strategy to prepare a novel IFN biobetter.
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