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1. Metabolic glycan labeling immobilizes dendritic cell membrane and enhances antitumor efficacy of dendritic cell vaccine

   https://doi.org/10.1038/s41467-023-40886-7  

   Han, Joonsu; Bhatta, Rimsha; Liu, Yusheng; Bo, Yang; Elosegui-Artola, Alberto; Wang, Hua (August 2023, Nature Communications)

   Abstract Dendritic cell (DC) vaccine was among the first FDA-approved cancer immunotherapies, but has been limited by the modest cytotoxic T lymphocyte (CTL) response and therapeutic efficacy. Here we report a facile metabolic labeling approach that enables targeted modulation of adoptively transferred DCs for developing enhanced DC vaccines. We show that metabolic glycan labeling can reduce the membrane mobility of DCs, which activates DCs and improves the antigen presentation and subsequent T cell priming property of DCs. Metabolic glycan labeling itself can enhance the antitumor efficacy of DC vaccines. In addition, the cell-surface chemical tags (e.g., azido groups) introduced via metabolic glycan labeling also enable in vivo conjugation of cytokines onto adoptively transferred DCs, which further enhances CTL response and antitumor efficacy. Our DC labeling and targeting technology provides a strategy to improve the therapeutic efficacy of DC vaccines, with minimal interference upon the clinical manufacturing process. 

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2. In Situ Dendritic Cell Recruitment and T Cell Activation for Cancer Immunotherapy

   https://doi.org/10.3389/fphar.2022.954955  

   Han, Joonsu; Bhatta, Rimsha; Liu, Yusheng; Bo, Yang; Wang, Hua (August 2022, Frontiers in Pharmacology)

   Cancer immunotherapy has shifted the paradigm for cancer treatment in the past decade, but new immunotherapies enabling the effective treatment of solid tumors are still greatly demanded. Here we report a pore-forming hydrogel-based immunotherapy that enables simultaneous recruitment of dendritic cells and in situ activation of T cells, for reshaping the immunosuppressive tumor microenvironment and amplifying cytotoxic T lymphocyte response. The injectable pore-forming hydrogel composed of porogen-dispersed alginate network can form a macroporous structure upon injection into mice, and enables controlled release of granulocyte-macrophage colony-stimulating factor (GM-CSF), a chemoattractant for recruiting dendritic cells, and epacadostat, an inhibitor of indoleamine 2, 3-dioxygenase for activating T cells. We show that gels loaded with GM-CSF and epacadostat, after peritumoral injection, can recruit massive dendritic cells in situ and activate effector T cells in the tumor tissues, resulting in enhanced frequency and activation status of dendritic cells, reduced numbers of regulatory T (Treg) cells, and increased CD8 + /Treg ratios in the tumor microenvironment. This hydrogel-based immunotherapy holds great promise for treating poorly-immunogenic solid tumors. 

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3. Dendritic cell force-migration coupling on aligned fiber networks

   https://doi.org/10.1016/j.bpj.2024.07.011  

   Hernandez-Padilla, Christian; Joosten, Ben; Franco, Aime; Cambi, Alessandra; van_den_Dries, Koen; Nain, Amrinder S (September 2024, Biophysical Journal)
4. Scale-up of a perfusion-based dendritic cell generation process

   https://doi.org/10.18609/cgti.2018.110  

   Kozbial, Andrew; Weinstein, Hope; Murthy, Shashi K.; Rossi, Jennifer M. (December 2018, Cell & gene therapy insights)

   Scale up of dendritic cell production is a critical challenge that is infeasible with current static culture systems such as well plates, T-flasks, and bags. We have developed a fully enclosed, sterile cell culture system, called EDEN, that allows for continuous perfusion of fresh differentiation medium into the cell culture cartridge and simultaneous removal of depleted medium. EDEN generated ca. 25 million immature dendritic cells (iDCs) per run with a yield, relative to seeded monocytes, of 20-30%. Immunophenotyping showed that EDEN generated iDCs were phenotypically similar to 6-well plate generated iDCs. Maturation of EDEN iDCs using a standard maturation cocktail was successful with upregulation of CD80/83/86 and downregulation of CD209. Computational fluid dynamics simulations aided the EDEN cartridge design to ensure proper differentiation medium perfusion. These results indicate that EDEN successfully generates clinically relevant numbers of iDCs in a single cell culture cartridge with fewer manual interventions compared to standard culture techniques. 

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5. Developing a Minimally Structured Mathematical Model of Cancer Treatment with Oncolytic Viruses and Dendritic Cell Injections

   https://doi.org/10.1155/2018/8760371  

   Gevertz, Jana L.; Wares, Joanna R. (October 2018, Computational and Mathematical Methods in Medicine)

   Mathematical models of biological systems must strike a balance between being sufficiently complex to capture important biological features, while being simple enough that they remain tractable through analysis or simulation. In this work, we rigorously explore how to balance these competing interests when modeling murine melanoma treatment with oncolytic viruses and dendritic cell injections. Previously, we developed a system of six ordinary differential equations containing fourteen parameters that well describes experimental data on the efficacy of these treatments. Here, we explore whether this previously developed model is the minimal model needed to accurately describe the data. Using a variety of techniques, including sensitivity analyses and a parameter sloppiness analysis, we find that our model can be reduced by one variable and three parameters and still give excellent fits to the data. We also argue that our model is not too simple to capture the dynamics of the data, and that the original and minimal models make similar predictions about the efficacy and robustness of protocols not considered in experiments. Reducing the model to its minimal form allows us to increase the tractability of the system in the face of parametric uncertainty. 

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