PMID- 36733607 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240102 IS - 2366-3987 (Electronic) IS - 2366-3987 (Linking) VI - 6 IP - 1 DP - 2023 Jan TI - Cell-free, Dendritic Cell-mimicking Extracellular Blebs for Molecularly Controlled Vaccination. LID - 2200125 [pii] LID - 10.1002/adtp.202200125 [doi] AB - Dendritic cells (DCs) are prime targets for vaccination and immunotherapy. However, limited control over antigen presentation at a desired maturation status in these plastic materials remains a fundamental challenge in efficiently orchestrating a controlled immune response. DC-derived extracellular vesicles (EVs) can overcome some of these issues, but have significant production challenges. Herein, we employ a unique chemically-induced method for production of DC-derived extracellular blebs (DC-EBs) that overcome the barriers of DC and DC-derived EV vaccines. DC-EBs are molecular snapshots of DCs in time, cell-like particles with fixed stimulatory profiles for controlled immune signalling. DC-EBs were produced an order of magnitude more quickly and efficiently than conventional EVs and displayed stable structural integrity and antigen presentation compared to live DCs. Multi-omic analysis confirmed DC-EBs are majorly pure plasma membrane vesicles that are homogeneous at the single-vesicle level, critical for safe and effective vaccination. Immature vs. mature molecular profiles on DC-EBs exhibited molecularly modulated immune responses compared to live DCs, improving remission and survival of tumor-challenged mice via generation of antigen-specific T cells. For the first time, DC-EBs make their case for use in vaccines and for their potential in modulating other immune responses, potentially in combination with other immunotherapeutics. FAU - Thone, Melissa N AU - Thone MN AD - Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA 92697, United States. AD - Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697, United States. FAU - Chung, Jee Young AU - Chung JY AD - Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697, United States. FAU - Ingato, Dominique AU - Ingato D AD - Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA 92697, United States. FAU - Lugin, Margaret L AU - Lugin ML AD - Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA 92697, United States. FAU - Kwon, Young Jik AU - Kwon YJ AD - Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA 92697, United States. AD - Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697, United States. AD - Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, United States. AD - Department of Biomedical Engineering, University of California, Irvine, CA 92697, United States. LA - eng GR - S10 OD021718/OD/NIH HHS/United States GR - S10 RR025496/RR/NCRR NIH HHS/United States GR - T32 AI007319/AI/NIAID NIH HHS/United States GR - P30 CA062203/CA/NCI NIH HHS/United States GR - P50 GM076516/GM/NIGMS NIH HHS/United States GR - S10 OD010794/OD/NIH HHS/United States PT - Journal Article DEP - 20220913 PL - Germany TA - Adv Ther (Weinh) JT - Advanced therapeutics JID - 101724632 PMC - PMC9888466 MID - NIHMS1839258 OTO - NOTNLM OT - Immunotherapy OT - cancer OT - dendritic cell OT - extracellular blebs OT - vaccine COIS- Conflict of interest statement: YJK is a co-founder of Jupiter Pharmaceuticals, Inc., a company based on applying extracellular blebs for drug delivery and general therapeutics. The potential conflict of interest is fully disclosed to and managed by the COI Oversight Committee at UC Irvine. EDAT- 2023/02/04 06:00 MHDA- 2023/02/04 06:01 PMCR- 2024/01/01 CRDT- 2023/02/03 02:00 PHST- 2023/02/03 02:00 [entrez] PHST- 2023/02/04 06:00 [pubmed] PHST- 2023/02/04 06:01 [medline] PHST- 2024/01/01 00:00 [pmc-release] AID - 2200125 [pii] AID - 10.1002/adtp.202200125 [doi] PST - ppublish SO - Adv Ther (Weinh). 2023 Jan;6(1):2200125. doi: 10.1002/adtp.202200125. Epub 2022 Sep 13.