{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:30:18Z","timestamp":1760232618477,"version":"build-2065373602"},"reference-count":77,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T00:00:00Z","timestamp":1668988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["19-74-30011","121031300044-5"],"award-info":[{"award-number":["19-74-30011","121031300044-5"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Russian state-funded budget project of ICBFM","award":["19-74-30011","121031300044-5"],"award-info":[{"award-number":["19-74-30011","121031300044-5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Cell-free antitumor vaccines represent a promising approach to immunotherapy of cancer. Here, we compare the antitumor potential of cell-free vaccines based on microvesicles derived from dendritic cells (DCs) with DC- and cationic-liposome-based vaccines using a murine model of drug-resistant lymphosarcoma RLS40 in vivo. The vaccines were the following: microvesicle vaccines\u2014cytochalasin B-induced membrane vesicles (CIMVs) obtained from DCs loaded with total tumor RNA using cholesterol\/spermine-containing cationic liposomes L or mannosylated liposomes ML; DC vaccines\u2014murine DCs loaded with total tumor-derived RNA using the same liposomes; and liposomal vaccines\u2014lipoplexes of total tumor-derived RNA with liposomes L or ML. Being non-hepatotoxic, CIMV- and DC-based vaccines administered subcutaneously exhibited comparable potential to stimulate highly efficient antitumor CTLs in vivo, whereas liposomal vaccines were 25% weaker CTL inducers. Nevertheless, the antitumor efficiencies of the different types of the vaccines were similar: sizes of tumor nodes and the number of liver metastases were significantly decreased, regardless of the vaccine type. Notably, the booster vaccination did not improve the overall antitumor efficacy of the vaccines under the study. CIMV- and DC- based vaccines more efficiently than liposome-based ones decreased mitotic activity of tumor cells and induced their apoptosis, stimulated accumulation of neutrophil inflammatory infiltration in tumor tissue, and had a more pronounced immunomodulatory activity toward the spleen and thymus. Administration of CIMV-, DC-, and liposome-based vaccines resulted in activation of Th1\/Th17 cells as well as the induction of positive immune checkpoint 4-1BBL and downregulation of suppressive immune checkpoints in a raw PD-1 &gt;&gt;&gt; TIGIT &gt; CTLA4 &gt; TIM3. We demonstrated that cell-free CIMV-based vaccines exhibited superior antitumor and antimetastatic activity in a tumor model in vivo. The obtained results can be considered as the basis for developing novel strategies for oncoimmunotherapy.<\/jats:p>","DOI":"10.3390\/pharmaceutics14112542","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T03:04:20Z","timestamp":1669086260000},"page":"2542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dendritic Cell-Derived Artificial Microvesicles Inhibit RLS40 Lymphosarcoma Growth in Mice via Stimulation of Th1\/Th17 Immune Response"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8381-1890","authenticated-orcid":false,"given":"Oleg V.","family":"Markov","sequence":"first","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentieva Ave. 8, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5729-9910","authenticated-orcid":false,"given":"Aleksandra V.","family":"Sen\u2019kova","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentieva Ave. 8, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1710-3925","authenticated-orcid":false,"given":"Islam S.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentieva Ave. 8, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3727-4905","authenticated-orcid":false,"given":"Elena V.","family":"Shmendel","sequence":"additional","affiliation":[{"name":"M.V. Lomonosov Institute of Fine Chemical Technologies, MIREA\u2014Russian Technological University, Vernadskogo Ave. 86, 119571 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5372-1325","authenticated-orcid":false,"given":"Mikhail A.","family":"Maslov","sequence":"additional","affiliation":[{"name":"M.V. Lomonosov Institute of Fine Chemical Technologies, MIREA\u2014Russian Technological University, Vernadskogo Ave. 86, 119571 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0134-0328","authenticated-orcid":false,"given":"Anastasiya L.","family":"Oshchepkova","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentieva Ave. 8, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeniy V.","family":"Brenner","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentieva Ave. 8, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4375-0269","authenticated-orcid":false,"given":"Nadezhda L.","family":"Mironova","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentieva Ave. 8, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4044-1049","authenticated-orcid":false,"given":"Marina A.","family":"Zenkova","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentieva Ave. 8, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Stefanski, H.E., Jonart, L., Goren, E., Mul\u00e9, J.J., and Blazar, B.R. (2018). A novel approach to improve immune effector responses post transplant by restoration of CCL21 expression. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0193461"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1007\/s00262-017-2028-5","article-title":"TGF-\u03b21-silenced leukemia cell-derived exosomes target dendritic cells to induce potent anti-leukemic immunity in a mouse model","volume":"66","author":"Huang","year":"2017","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1158\/0008-5472.CAN-16-2089","article-title":"CD40 signaling drives potent cellular immune responses in heterologous cancer vaccinations","volume":"77","author":"Nimanong","year":"2017","journal-title":"Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1158\/2326-6066.CIR-16-0309","article-title":"Depletion of tumor-associated macrophages with a CSF-1R kinase inhibitor enhances antitumor immunity and survival induced by DC immunotherapy","volume":"5","author":"Dammeijer","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1758835920922034","DOI":"10.1177\/1758835920922034","article-title":"Bin Combination therapy with dendritic cell vaccine and programmed death ligand 1 immune checkpoint inhibitor for hepatocellular carcinoma in an orthotopic mouse model","volume":"12","author":"Teng","year":"2020","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1007\/s00262-018-2232-y","article-title":"Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in glioblastoma: An exploratory randomized phase II clinical trial","volume":"67","author":"Yao","year":"2018","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1182\/blood-2017-04-780155","article-title":"Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia","volume":"130","author":"Anguille","year":"2017","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"27","DOI":"10.32607\/20758251-2017-9-3-27-38","article-title":"Antitumor vaccines based on dendritic cells: From experiments using animal tumor models to clinical trials","volume":"9","author":"Markov","year":"2017","journal-title":"Acta Nat."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1159\/000512451","article-title":"Recent Advances in Good Manufacturing Practice-Grade Generation of Dendritic Cells","volume":"47","author":"Cunningham","year":"2020","journal-title":"Transfus. Med. Hemotherapy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.jcyt.2019.07.004","article-title":"Preservation of cell-based immunotherapies for clinical trials","volume":"21","author":"Li","year":"2019","journal-title":"Cytotherapy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/bs.ircmb.2019.08.005","article-title":"Dendritic cell extracellular vesicles","volume":"349","author":"Kowal","year":"2019","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1172\/JCI81137","article-title":"Dendritic cell-derived exosomes for cancer therapy","volume":"126","author":"Pitt","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s13046-020-01781-x","article-title":"Dexosomes as a cell-free vaccine for cancer immunotherapy","volume":"39","author":"Nikfarjam","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.3389\/fphar.2019.01152","article-title":"Immunotherapy based on dendritic cell-targeted\/-derived extracellular vesicles\u2014A novel strategy for enhancement of the anti-tumor immune response","volume":"10","author":"Markov","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1479-5876-3-9","article-title":"A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer","volume":"3","author":"Morse","year":"2005","journal-title":"J. Transl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1479-5876-3-10","article-title":"Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: Results of the first phase 1 clinical trial","volume":"3","author":"Escudier","year":"2005","journal-title":"J. Transl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e1071008","DOI":"10.1080\/2162402X.2015.1071008","article-title":"Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC","volume":"5","author":"Besse","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"789","DOI":"10.7150\/thno.18133","article-title":"Progress in exosome isolation techniques","volume":"7","author":"Li","year":"2017","journal-title":"Theranostics"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Oshchepkova, A., Neumestova, A., Matveeva, V., Artemyeva, L., Morozova, K., Kiseleva, E., Zenkova, M., and Vlassov, V. (2019). Cytochalasin-B-inducible nanovesicle mimics of natural extracellular vesicles that are capable of nucleic acid transfer. Micromachines, 10.","DOI":"10.3390\/mi10110750"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"17095","DOI":"10.1038\/s41598-017-16609-6","article-title":"Exosomes from antigen-pulsed dendritic cells induce stronger antigen-specific immune responses than microvesicles in vivo","volume":"7","author":"Wahlund","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1158\/0008-5472.CAN-12-3918","article-title":"Synergistic induction of adaptive antitumor immunity by codelivery of antigen with \u03b1-galactosylceramide on exosomes","volume":"73","author":"Gehrmann","year":"2013","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17622","DOI":"10.1038\/srep17622","article-title":"TLR-3 stimulation improves anti-tumor immunity elicited by dendritic cell exosome-based vaccines in a murine model of melanoma","volume":"5","author":"Damo","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1016\/0006-2952(94)90318-2","article-title":"Cytochalasin B may shorten actin filaments by a mechanism independent of barbed end capping","volume":"47","author":"Theodoropoulos","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10740","DOI":"10.1038\/s41598-020-67563-9","article-title":"Immunosuppressive properties of cytochalasin B-induced membrane vesicles of mesenchymal stem cells: Comparing with extracellular vesicles derived from mesenchymal stem cells","volume":"10","author":"Gomzikova","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chulpanova, D.S., Gilazieva, Z.E., Kletukhina, S.K., Aimaletdinov, A.M., Garanina, E.E., James, V., Rizvanov, A.A., and Solovyeva, V.V. (2021). Cytochalasin B-Induced membrane vesicles from human mesenchymal stem cells overexpressing IL2 are able to stimulate CD8+ T-Killers to kill human triple negative breast cancer cells. Biology, 10.","DOI":"10.3390\/biology10020141"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gomzikova, M.O., Kletukhina, S.K., Kurbangaleeva, S.V., Neustroeva, O.A., Vasileva, O.S., Garanina, E.E., Khaiboullina, S.F., and Rizvanov, A.A. (2020). Mesenchymal stem cell derived biocompatible membrane vesicles demonstrate immunomodulatory activity inhibiting activation and proliferation of human mononuclear cells. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12060577"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7053623","DOI":"10.1155\/2018\/7053623","article-title":"Evaluation of Cytochalasin B-Induced Membrane Vesicles Fusion Specificity with Target Cells","volume":"2018","author":"Gomzikova","year":"2018","journal-title":"Biomed Res. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"70496","DOI":"10.18632\/oncotarget.19723","article-title":"Cytochalasin B-induced membrane vesicles convey angiogenic activity of parental cells","volume":"8","author":"Gomzikova","year":"2017","journal-title":"Oncotarget"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/nm0598-594","article-title":"Eradication of established murine tumors using a novel cell-free vaccine: Dendritic cell-derived exosomes","volume":"4","author":"Zitvogel","year":"1998","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1002\/eji.200535615","article-title":"Direct exosome stimulation of peripheral human T cells detected by ELISPOT","volume":"36","author":"Admyre","year":"2006","journal-title":"Eur. J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1196\/annals.1378.090","article-title":"Animal model of drug-resistant tumor progression","volume":"1091","author":"Mironova","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jconrel.2011.11.034","article-title":"Novel cationic liposomes provide highly efficient delivery of DNA and RNA into dendritic cell progenitors and their immature offsets","volume":"160","author":"Markov","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jconrel.2015.06.028","article-title":"Multicomponent mannose-containing liposomes efficiently deliver RNA in murine immature dendritic cells and provide productive anti-tumour response in murine melanoma model","volume":"213","author":"Markov","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1007\/s11172-010-0071-x","article-title":"Synthesis of polycationic lipids based on cholesterol and spermine","volume":"59","author":"Petukhov","year":"2010","journal-title":"Russ. Chem. Bull."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1007\/s11172-012-0194-3","article-title":"Synthesis of mannose-containing neoglycolipids as a component of targeted delivery system for transfer of nucleic acids into antigen-presenting cells","volume":"61","author":"Timakova","year":"2012","journal-title":"Russ. Chem. Bull."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1134\/S0026893317010137","article-title":"Systemic delivery of complexes of melanoma RNA with mannosylated liposomes activates highly efficient murine melanoma-specific cytotoxic T cells in vivo","volume":"51","author":"Markov","year":"2017","journal-title":"Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Oshchepkova, A., Markov, O., Evtushenko, E., Chernonosov, A., Kiseleva, E., Morozova, K., Matveeva, V., Artemyeva, L., Vlassov, V., and Zenkova, M. (2021). Tropism of extracellular vesicles and cell-derived nanovesicles to normal and cancer cells: New perspectives in tumor-targeted nucleic acid delivery. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13111911"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Dias, M.V.S., Martins, V.R., and Hajj, G.N.M. (2016). Stress-Inducible Protein 1 (STI1): Extracellular Vesicle Analysis and Quantification, Humana Press.","DOI":"10.1007\/978-1-4939-3804-9_11"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Markov, O.V., Mironova, N.L., Sennikov, S.V., Vlassov, V.V., and Zenkova, M.A. (2015). Prophylactic dendritic cell-based vaccines efficiently inhibit metastases in murine metastatic melanoma. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136911"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s00262-007-0350-z","article-title":"Activation and route of administration both determine the ability of bone marrow-derived dendritic cells to accumulate in secondary lymphoid organs and prime CD8+ T cells against tumors","volume":"57","author":"Huck","year":"2008","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"269","DOI":"10.4110\/in.2012.12.6.269","article-title":"Dendritic Cell (DC) Vaccine in Mouse Lung Cancer Minimal Residual Model; Comparison of Monocyte-derived DC vs. Hematopoietic Stem Cell Derived-DC","volume":"12","author":"Baek","year":"2012","journal-title":"Immune Netw."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nature21428","article-title":"Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination","volume":"543","author":"Pardi","year":"2017","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e2005191118","DOI":"10.1073\/pnas.2005191118","article-title":"Delivery of mRNA vaccine with a lipid-like material potentiates antitumor efficacy through toll-like receptor 4 signaling","volume":"118","author":"Zhang","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1158\/0008-5472.CAN-11-2957","article-title":"Preclinical evaluation of TriMix and antigen mRNA-based antitumor therapy","volume":"72","author":"Goyvaerts","year":"2012","journal-title":"Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1038\/mt.2016.161","article-title":"Type I interferons interfere with the capacity of mRNA lipoplex vaccines to elicit Cytolytic T cell responses","volume":"24","author":"Pollard","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.actbio.2020.08.008","article-title":"Anti-CTLA-4 antibody-functionalized dendritic cell-derived exosomes targeting tumor-draining lymph nodes for effective induction of antitumor T-cell responses","volume":"115","author":"Phung","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"120112","DOI":"10.1016\/j.biomaterials.2020.120112","article-title":"Antitumor immunity by small extracellular vesicles collected from activated dendritic cells through effective induction of cellular and humoral immune responses","volume":"252","author":"Matsumoto","year":"2020","journal-title":"Biomaterials"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6867","DOI":"10.1016\/j.biomaterials.2010.05.027","article-title":"The systemic toxicity of positively charged lipid nanoparticles and the role of Toll-like receptor 4 in immune activation","volume":"31","author":"Kedmi","year":"2010","journal-title":"Biomaterials"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/j.addr.2012.05.009","article-title":"Cationic lipids activate intracellular signaling pathways","volume":"64","author":"Lonez","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_50","first-page":"721612","article-title":"The Toxic Effects of Polychemotherapy onto the Liver Are Accelerated by the Upregulated MDR of Lymphosarcoma","volume":"2012","author":"Mironova","year":"2012","journal-title":"ISRN Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.4161\/cc.25164","article-title":"Ribonuclease binase inhibits primary tumor growth and metastases via apoptosis induction in tumor cells","volume":"12","author":"Mironova","year":"2013","journal-title":"Cell Cycle"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/jlb.67.5.607","article-title":"The critical role of CD40\/CD40L in the CD4-dependent generation of CD8+ T cell immunity","volume":"67","author":"Clarke","year":"2000","journal-title":"J. Leukoc. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8083","DOI":"10.4049\/jimmunol.180.12.8083","article-title":"Full Development of Th2 Immunity Requires Both Innate and Adaptive Sources of CD154","volume":"180","author":"Jenkins","year":"2008","journal-title":"J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"101528","DOI":"10.1016\/j.smim.2021.101528","article-title":"CD40-CD154: A perspective from type 2 immunity","volume":"53","year":"2021","journal-title":"Semin. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"13015","DOI":"10.1021\/acsomega.9b00489","article-title":"Codelivery of mRNA with \u03b1-galactosylceramide using a new lipopolyplex formulation induces a strong antitumor response upon intravenous administration","volume":"4","author":"Guevara","year":"2019","journal-title":"ACS Omega"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1038\/s41587-019-0247-3","article-title":"Delivery of mRNA vaccines with heterocyclic lipids increases anti-tumor efficacy by STING-mediated immune cell activation","volume":"37","author":"Miao","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ymthe.2017.10.020","article-title":"Combination Immunotherapy of MUC1 mRNA Nano-vaccine and CTLA-4 Blockade Effectively Inhibits Growth of Triple Negative Breast Cancer","volume":"26","author":"Liu","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"104143","DOI":"10.1016\/j.cellimm.2020.104143","article-title":"Intranasal delivery of cationic liposome-protamine complex mRNA vaccine elicits effective anti-tumor immunity","volume":"354","author":"Mai","year":"2020","journal-title":"Cell. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"9815","DOI":"10.1021\/acsnano.8b00966","article-title":"Dendritic Cell Targeting mRNA Lipopolyplexes Combine Strong Antitumor T-Cell Immunity with Improved Inflammatory Safety","volume":"12","author":"Bialkowski","year":"2018","journal-title":"ACS Nano"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jconrel.2020.08.023","article-title":"DP7-C-modified liposomes enhance immune responses and the antitumor effect of a neoantigen-based mRNA vaccine","volume":"328","author":"Zhang","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_61","first-page":"1655","article-title":"Broadening the Message: A Nanovaccine Co-loaded with Messenger RNA and \u03b1-GalCer Induces Antitumor Immunity through Conventional and Natural Killer T Cells","volume":"13","author":"Verbeke","year":"2019","journal-title":"ACS Nano"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"21782","DOI":"10.1039\/C9NR05475H","article-title":"Hybrid nanovaccine for the co-delivery of the mRNA antigen and adjuvant","volume":"11","author":"Yang","year":"2019","journal-title":"Nanoscale"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1021\/ja044605x","article-title":"Investigating cellular signaling reactions in single attoliter vesicles","volume":"127","author":"Pick","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Gomzikova, M.O., Zhuravleva, M.N., Vorobev, V.V., Salafutdinov, I.I., Laikov, A.V., Kletukhina, S.K., Martynova, E.V., Tazetdinova, L.G., Ntekim, A.I., and Khaiboullina, S.F. (2020). Angiogenic activity of cytochalasin B-induced membrane vesicles of human mesenchymal stem cells. Cells, 9.","DOI":"10.1101\/646398"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"101664","DOI":"10.1016\/j.tice.2021.101664","article-title":"Cytochalasin B-induced membrane vesicles from human mesenchymal stem cells overexpressing TRAIL, PTEN and IFN-\u03b21 can kill carcinoma cancer cells","volume":"73","author":"Chulpanova","year":"2021","journal-title":"Tissue Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e00616","DOI":"10.1016\/j.btre.2021.e00616","article-title":"Storage stability and delivery potential of cytochalasin B induced membrane vesicles","volume":"30","author":"Kletukhina","year":"2021","journal-title":"Biotechnol. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s12668-021-00931-5","article-title":"Analysis of the Interaction of Human Neuroblastoma Cell-Derived Cytochalasin B Induced Membrane Vesicles with Mesenchymal Stem Cells Using Imaging Flow Cytometry","volume":"12","author":"Solovyeva","year":"2022","journal-title":"Bionanoscience"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2102643","DOI":"10.1002\/smll.202102643","article-title":"Antigen-Specific Stimulation and Expansion of CAR-T Cells Using Membrane Vesicles as Target Cell Surrogates","volume":"17","author":"Ukrainskaya","year":"2021","journal-title":"Small"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s00262-012-1377-3","article-title":"The immunological response and post-treatment survival of DC-vaccinated melanoma patients are associated with increased Th1\/Th17 and reduced Th3 cytokine responses","volume":"62","author":"Segal","year":"2013","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_70","first-page":"337","article-title":"Enhancement of anti-tumor immunity by high levels of Th1 and Th17 with a combination of dendritic cell fusion hybrids and regulatory T cell depletion in pancreatic cancer","volume":"22","author":"Yamamoto","year":"2009","journal-title":"Oncol. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1007\/s00262-011-1063-x","article-title":"Vaccination with CD133 + melanoma induces specific Th17 and Th1 cell-mediated antitumor reactivity against parental tumor","volume":"60","author":"Miyabayashi","year":"2011","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s12967-020-02328-6","article-title":"Cytokine network analysis of immune responses before and after autologous dendritic cell and tumor cell vaccine immunotherapies in a randomized trial","volume":"18","author":"Nistor","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e1356964","DOI":"10.1080\/2162402X.2017.1356964","article-title":"Exploiting a new strategy to induce immunogenic cell death to improve dendritic cell-based vaccines for lymphoma immunotherapy","volume":"6","author":"Montico","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1517\/14712598.2011.554812","article-title":"Dendritic cell vaccination against ovarian cancer-tipping the Treg\/T H17 balance to therapeutic advantage?","volume":"11","author":"Cannon","year":"2011","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"527","DOI":"10.3390\/vaccines1040527","article-title":"Dendritic Cell-Induced Th1 and Th17 Cell Differentiation for Cancer Therapy","volume":"1","author":"Terhune","year":"2013","journal-title":"Vaccines"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.immuni.2009.09.014","article-title":"T Helper 17 Cells Promote Cytotoxic T Cell Activation in Tumor Immunity","volume":"31","author":"Muranski","year":"2009","journal-title":"Immunity"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4063","DOI":"10.4049\/jimmunol.0902609","article-title":"Induction of Th17 Cells in the Tumor Microenvironment Improves Survival in a Murine Model of Pancreatic Cancer","volume":"185","author":"Gnerlich","year":"2010","journal-title":"J. Immunol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/11\/2542\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:22:59Z","timestamp":1760145779000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/11\/2542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,21]]},"references-count":77,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["pharmaceutics14112542"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14112542","relation":{},"ISSN":["1999-4923"],"issn-type":[{"type":"electronic","value":"1999-4923"}],"subject":[],"published":{"date-parts":[[2022,11,21]]}}}