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Abstract: Chimeric antigen receptor (CAR) T-cell therapies have demonstrated transformative efficacy in treating B-cell malignancies. However, high costs and manufacturing complexities hinder their widespread use. To overcome these hurdles, we have developed the VivoVec platform, a lentiviral vector capable of generating CAR T cells in vivo. Here, we describe the incorporation of T-cell activation and costimulatory signals onto the surface of VivoVec particles (VVPs) in the form of a multidomain fusion protein and show enhanced in vivo transduction and improved CAR T-cell antitumor functionality. Furthermore, in the absence of lymphodepleting chemotherapy, administration of VVPs into nonhuman primates resulted in the robust generation of anti-CD20 CAR T cells and the complete depletion of B cells for >10 weeks. These data validate the VivoVec platform in a translationally relevant model and support its transition into human clinical testing, offering a paradigm shift in the field of CAR T-cell therapies., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

eIF4E plays a conserved role in initiating protein synthesis, but with multiple eIF4E isoforms present in many organisms, these proteins also adopt specialized functions. Previous RNAi studies showed that ife-3, encoding the sole canonical eIF4E isoform of Caenorhabditis elegans, is essential for viability. Using ife-3 gene mutations, we show here that it is maternal ife-3 function that is essential for embryogenesis, but ife-3 null progeny of heterozygous animals are viable. We find that zygotic ife-3 function promotes body growth and regulates germline development in hermaphrodite worms. Specifically, the normal transition from spermatogenesis to oogenesis in the hermaphrodite germline fails in ife-3 mutants. This failure to switch is reversed by inhibiting expression of the key masculinizing gene, fem-3, suggesting ife-3 resembles a growing number of genes that promote the sperm/oocyte switch by acting genetically as upstream inhibitors of fem-3., (© 2015. Published by The Company of Biologists Ltd.)