Year: 2026
Type: preprint
Abstract: Recombinant cytokine therapeutics, among the earliest clinical immunotherapies, have yet to reach their full potential despite bioengineering advances. Here, we propose a novel approach focusing on in vivo cytokine production by immune cells in lymphoid organs to mimic these proteins’ physiological function. We developed apolipoprotein nanoparticles (aNPs) to deliver mRNA encoding cytokines, such as interleukin-2 (IL-2), to monocytes in secondary lymphoid tissues. To this end, we engineered a scalable manufacturing process that yields stable aNP- mRNA formulations suitable for long-term storage. Intravenous aNP-mRNA-IL-2 administration in mice led to sustained IL-2 production in the spleen and lymph nodes, significantly inhibiting tumor growth in B16F10 melanoma and MC38 colon cancer models. We confirmed translational potential through clinical positron emission tomography (PET) imaging and functional cytokine production in non-human primates, and validated aNP-mRNA efficacy on primary immune cells from cancer patients. This mRNA-based cytokine delivery to lymphoid organs offers a promising strategy to enhance cytokine immunotherapy for cancer and potentially other immune-mediated diseases, including autoimmunity, cardiovascular disease, and neurodegenerative conditions.
Source: Research Square
Authors: Willem Mulder, Tom Anbergen, Yuri van Elsas, Stijn Hofstraat, Merel Hendrikx, Jeroen Deckers, Iris Versteeg, Gijs Ros, Myrthe Kapteijns, Branca Bartelet, Robby Zwolsman, Mirre Trines, Daniek Hoorn, Scott Bex, Pepijn van Houten, Athanasios Ziogas, Cristina Grao-Roldán, Giulia Davighi, William Wang, Georgios Soultanidis, Ali Salehi Farid, Yoon Ho Lee, Noortje Voeten, Jurgen Piek, Gerben Franssen, Sandra Heskamp, Henk Janssen, Michel Fransen, Mireille Langouo-Fontsa, Andrea Garavello, Panagiotis Karras, Romana Netea-Maier, Carlos Pérez-Medina, Zahi Fayad, Mandy van Leent, Abraham Teunissen, Mohammad Rashidian, Ewelina Kluza, Yohana C. Toner, Bram Priem, Joost Kreijtz, Thijs Beldman, Mihai Netea, Roy van der Meel
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7140190367