Projektbeschreibung
Subkutane Verabreichung von Medikamenten zur Immuntherapie
Die intravenöse Verabreichung bietet eine schnelle und präzise Verabreichung von Medikamenten oder Flüssigkeiten direkt in den Blutkreislauf, was einen schnellen Wirkungseintritt und eine genaue Dosierung gewährleistet, was besonders für Menschen von Vorteil ist, die keine oralen Medikamente einnehmen können. Allerdings ist die intravenöse Verabreichung mit Risiken verbunden, darunter potenzielle Infektionen, Venenschäden oder -reizungen und die Möglichkeit, dass Medikamente austreten. Obwohl die subkutane Verabreichung als vielversprechende Alternative gilt, ist die Entwicklung von biologischen Arzneimitteln und Zelltherapien, die für die subkutane Verabreichung geeignet sind, begrenzt. Das vom Europäischen Forschungsrat finanzierte Projekt Sub-NK zielt darauf ab, funktionalisierte Hydrogele für die kontrollierte Freisetzung modifizierter natürlicher Killerzellen zu entwickeln und damit den Weg zur Etablierung des subkutanen Wegs für die Krebsimmuntherapie zu ebnen.
Ziel
This PoC project seeks to develop a simple-to-implement self-assembled and injectable hydrogel material for the controlled co-delivery of our simili-CAR NK cells and stimulatory cytokines to improves treatment of both solid and liquid tumors. Similar to biologics delivery where monoclonal antibodies (mAbs) are commonly administered by IV infusion due to regulatory criteria favoring such route which had limited confounding factors, the IV administration remains responsible for some over costs and clinical challenges including the need for dedicated infusion facilities, aseptic preparation of required infusion batches, extended infusion times, potential difficulties and risks with IV catheter. The subcutaneous (SC) administration is deemed to overcome many of these challenges and might appear as an attractive alternative to the IV administration. In addition, the SC route used for mAb administration was received with an overwhelming preference according to patients despite limited and reversible local adverse events induced by the rHuPH20. Alternative solutions are being evaluated through clinical trials such as the direct SC injection of mAbs without recombinant human hyaluronidase or using novel enzymes but none are currently being clinically-developed for cellular therapies. Moreover, those alternative SC methods induced large pharmacokinetic heterogeneity between patients confirming the need to develop novel alternative approaches to accelerate the development of SC mAbs formulation. Hence, in parallel to the biological approach, chemistry-based approaches, such as hydrogels have been proposed. However, to date, none of them successfully managed to be translated to the clinic; this can be explained by the absence of full biodegradability after injection or/and potential poor biocompatibility inducing inflammatory responses. Here, we sought to develop a novel formulation of functionalized-chitosans for controlled release of modified NK cells.
Wissenschaftliches Gebiet
Schlüsselbegriffe
Programm/Programme
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thema/Themen
Finanzierungsplan
HORIZON-ERC-POC - HORIZON ERC Proof of Concept GrantsGastgebende Einrichtung
67065 Strasbourg
Frankreich