Casey W Shuptrine, Yuhui Chen, Jayalakshmi Miriyala, Karen Lenz, Danielle Moffett, Thuy-Ai Nguyen, Jenn Michaux, Kristen Campbell, Connor Smith, Marc Morra, Yisel Rivera-Molina, Noah Murr, Sarah Cooper, Ashlyn McGuire, Vishruti Makani, Nathan Oien, Jeffrey T Zugates, Suresh de Silva, Taylor H Schreiber, Seymour de Picciotto, George Fromm
Lipid nanoparticle (LNP)-encapsulated mRNA has been used for in vivo production of several secreted protein classes, such as IgG, and has enabled the development of personalized vaccines in oncology. Establishing the feasibility of delivering complex multi-specific modalities that require higher-order structures important for their function could help expand the use of mRNA/LNP biologic formulations. Here, we evaluated whether in vivo administration of mRNA/LNP formulations of SIRPα-Fc-CD40L and TIGIT-Fc-LIGHT could achieve oligomerization and extend exposure, on-target activity, and anti-tumor responses comparable to that of the corresponding recombinant fusion proteins...
February 21, 2024: Cancer Research