SHANG Yi-Yuan, GAO Meng-Yuan, WANG Yi-Fan, LI Chao-Jie, YU Lu-Ying, QIAN Jia-Miao, WANG Xu-Jiao, YANG Li-Dong, HUANG Rui-Zhi, DONG Xin-Wang, SUN Jing*, WU Yong-Shu*
College of Animal Science and Technology• College of Veterinary Medicine, Zhejiang A&F University/Key Laboratory of Applied Biotechnology on Animal Science & Veterinary Medicine of Zhejiang Province/Zhejiang Engineering Research Center for Veterinary Diagnostics & Advanced Technology/Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management/Belt and Road International Joint Laboratory for One Health and Food Safety/China-Australia Joint Laboratory for Animal Health Big Data Analytics, Hangzhou 311300, China
Abstract：Cancer is a major disease that seriously threatens the health of humans and animals, and its treatment strategies are still under continuous exploration. Anti-tumor nanovaccines represent an emerging immunotherapy following monoclonal antibodies, immune checkpoint inhibitors, and adoptive cell therapy. This approach utilizes nanomaterials as carriers to assemble functional components such as antigens and adjuvants into nano-scale vaccine formulations. By mimicking pathogen characteristics, these vaccines effectively activate the host immune system's surveillance and clearance functions against tumor cells. This article systematically reviews recent advances in anti-tumor nanovaccines from four aspects: nanovaccine materials, tumor antigens, adjuvants, and combination therapies for enhanced efficacy. Based on this foundation, it particularly summarizes current research and applications of nanovaccines for tumors in livestock and poultry, and aims to provide theoretical references for the prevention and control of animal tumors and tumor immunotherapy in agricultural animals.
[1] Arranz-Herrero J, Marquez-Cantudo L, Rius-Rocabert S, et al.2026. STING activation by teniposide: A potential direct mechanism beyond cGAS stimulation[J]. Frontiers in Immunology, 16: 1677836. [2] Baden L R, El Sahly H M, Essink B, et al.2021. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine[J]. The New England Journal of Medicine, 384(5): 403-416. [3] Bai M, Dong H, Su X, et al.2019. Hollow mesoporous silica nanoparticles as delivery vehicle of Foot-and-mouth disease virus-like particles induce persistent immune responses in guinea pigs[J]. Journal of Medical Virology, 91(6): 941-948. [4] Bi Q, Yang H, Li S, et al.2026. Hybrid lipoplex co-delivering siPD-L1/miR-140-5p reverses T cell exhaustion via post-transcriptional regulation for in situ photothermal vaccination[J]. Nanoscale, 18: 2132-2143. [5] BioNTech.2026. BioNTech provides update on phase 2 clinical trial of autogene cevumeran in resected colorectal cancer. form 6-K, exhibit 99.1[EB/OL]. Filed August 28. (https://www.biontech.com/int/en/home/mediaroom/news/statements/2026/08/BioNTech-Provides-Update-on-Phase-2-Clinical-Trial-of-Autogene-Cevumeran-in-Resected-Colorectal-Cancer.html) [6] Chen G, Li X, Li R, et al.2023. Chemotherapy-induced neoantigen nanovaccines enhance checkpoint blockade cancer immunotherapy[J]. ACS Nano, 18(23): 15264-15277. [7] Chen L, Kang Z, Shen J, et al.2024. An emerging antibacterial nanovaccine for enhanced chemotherapy by selectively eliminating tumor-colonizing bacteria[J]. Science Bulletin, 69(16): 2565-2579. [8] Choi S H, Zhang B.2025. PepQueryMHC: Rapid and comprehensive tumor antigen prioritization from immunopeptidomics data[J]. Genome Biology, 26: 434. [9] Chu Y, Liu Q, Wei J, Liu B.2018. Personalized cancer neoantigen vaccines come of age[J]. Theranostics, 8: 4238-4246. [10] Chung D J, Shah N, Pasquini M C, et al.2023. Randomized phase II trial of dendritic cell/myeloma fusion vaccine with lenalidomide maintenance after upfront autologous HCT for multiple myeloma: BMT CTN 1401[J]. Clinical Cancer Research, 29(23): 4784-4796. [11] Circelli L, Tornesello M, Buonaguro F M, et al.2017. Use of adjuvants for immunotherapy[J]. Human Vaccines & Immunotherapeutics, 13(8): 1774-1777. [12] Cuevas M V R, Hardy M P, Larouche J D, et al.2023. BamQuery: A Proteogenomic tool to explore the immunopeptidome and prioritize actionable tumor antigens[J]. Genome Biology, 24: 188. [13] Del Cacho E, Gallego M, Lee S H, et al.2011. Induction of protective immunity against Eimeria tenella infection using antigen-loaded dendritic cells (DC) and DC-derived exosomes[J]. Vaccine, 29(21): 3818-3825. [14] Del Cacho E, Gallego M, Lillehoj H S, et al.2016. Induction of protective immunity against experimental Eimeria tenella infection using serum exosomes[J]. Veterinary Parasitology, 224: 16. [15] Devaraji M, Cheriyan B V.2025. Immune-based cancer therapies: mechanistic insights, clinical progress, and future directions[J]. Journal of the Egyptian National Cancer Institute, 37(1): 62. [16] Du J, Luo C, Liu Y, et al.2025. PD-L1-targeted polymer-peptide-immune nanomedicine synergizes radiotherapy for durable tumor control[J]. Bioactive Materials, 29: 624-638. [17] Everest Medicines.2025. Everest Medicines announces first patient enrolled in a global multi-center phase I clinical trial of tumor-associated antigen cancer vaccine EVM14[EB/OL]. Published October 14. (https://www.everestmedicines.com/news/everest-medicines-announces-first-patient/c4359536-ed70-4905-9687-254cb913f6f4) [18] Feng J, He D, Chen J, et al.2025a. Cell membrane biomimetic nanoplatforms: A new strategy for immune escape and precision targeted therapy[J]. Materials Today Bio, 35: 102343. [19] Feng R, Xue R Y, Liu C, et al.2025b. RBD-displaying OMV nanovaccine boosts immunity against SARS-CoV-2[J]. Journal of Nanobiotechnology, 23(1): 97. [20] Finn O.2026. Opportunity knocking: Shared tumor-associated antigen vaccines against global cancer pandemic[J]. Journal for ImmunoTherapy of Cancer, 14: e013130. [21] Fu Z M, Zhang Y F, Chen X L, et al.2023. A versatile nanoplatform based on metal-phenolic networks inhibiting tumor growth and metastasis by combined starvation / chemodynamic / immunotherapy[J]. Advanced Functional Materials, 33(7): 2211869. [22] Gao F, Lu D, Wei Y, et al.2025. Vaccine-integrated nanoplatform for lactate-activatable chemo/chemodynamic therapy and multiple immune regulations of tumor[J]. Advanced Healthcare Materials, 14(12): e202401234. [23] Grigoryan L, Lee A, Walls A C, et al.2022. Adjuvanting a subunit SARS-CoV-2 vaccine with clinically relevant adjuvants induces durable protection in mice[J]. npj Vaccines, 7(1): 55. [24] Hamidian K, Sarani M, Oveisi A R.2026. Biosynthesis of CeO2@UiO-66-NH2 nano-carrier for enhanced doxorubicin delivery and cytotoxicity assessment in HepG2 liver cancer cells[J]. Materials Today Communications, 51: 114646. [25] Han S L, Wang W J, Wang S F, et al.2021. Tumor microenvironment remodeling and tumor therapy based on M2-like tumor associated macrophage-targeting nano-complzexes[J]. Theranostics, 11(6): 2892-2916. [26] Herck S V, Feng B, Tang L.2021. Delivery of STING agonists for adjuvating subunit vaccines[J]. Advanced Drug Delivery Reviews, 179: 114020. [27] Hou X, Zaks T, Langer R, et al.2021. Lipid nanoparticles for mRNA delivery[J]. Nature Reviews Materials, 6(12): 1078-1094. [28] Huang L X, Rong Y, Tang X, et al.2022. Engineered exosomes as an in-situ DC-primed vaccine to boost antitumor immunity in breast cancer[J]. Molecular Cancer, 21(1): 45. [29] Hwang D, Erdman M C, Adhikari S, et al.2026. HLA-Shuttle: A system for enhancing antigen presentation in immunologically cold tumors[J]. Science Advances, 12(1): eaeb0821. [30] Ivanov K, Garanina E, Rizvanov A, et al.2020. Inflammasomes as targets for adjuvants[J]. Pathogens, 9(4): 252. [31] Jain R K, Stylianopoulos T.2010. Delivering nanomedicine to solid tumors[J]. Nature Reviews Clinical Oncology, 7(11): 653-664. [32] Jin M, Huo D, Sun J, et al.2024. Enhancing immune responses of ESC-based TAA cancer vaccines with a novel OMV delivery system[J]. Journal of Nanobiotechnology, 22(1): 143. [33] Joshi D C, Sharma A, Prasad S, et al.2024. Novel therapeutic agents in clinical trials: Emerging approaches in cancer therapy[J]. Discover Oncology, 15(1): 342. [34] Kang D D, Hou X C, Wang L M, et al.2024. Engineering LNPs with polysarcosine lipids for mRNA delivery[J]. Bioactive Materials, 37: 86-93. [35] Khattak A, Carlino M S, Khattak A, et al.2026. Intismeran autogene plus pembrolizumab versus pembrolizumab alone in high-risk resected melanoma: 5-year update of the randomized phase IIb KEYNOTE-942 study[J]. Journal of Clinical Oncology. 44(26): 2482-2489. [36] Kim H, Griffith T S, Panyam J.2019. Poly (d, l-lactide-co-glycolide) nanoparticles as delivery platforms for TLR7/8 agonist-based cancer vaccine[J]. Journal of Pharmacology and Experimental Therapeutics, 381(2): 266-276. [37] Leong K Y, Tham S K, Poh C L, et al.2025. Revolutionizing immunization: A comprehensive review of mRNA vaccine technology and applications[J]. Virology Journal, 22: 71. [38] Li Q, Teng Z G, Tao J, et al.2022. Elastic nanovaccine enhances dendritic cell-mediated tumor immunotherapy[J]. Small, 18(32): 2201108. [39] Li Y W, Fang M X, Yu H T, et al.2025. Neoantigen enriched biomimetic nanovaccine for personalized cancer immunotherapy[J]. Nature Communications, 16: 4783. [40] Liang X, Wu G, Chen R, et al.2025. Tumor antigen-coated two-dimensional black phosphorus as a nanovaccine for synergistic cancer photothermal therapy and immunotherapy[J]. ACS Applied Bio Materials, 8(2): 912-923. [41] Liau L M, Ashkan K, Brem S, et al.2023. Association of autologous tumor lysate-loaded dendritic cell vaccination with extension of survival among patients with newly diagnosed and recurrent glioblastoma: A phase 3 prospective externally controlled cohort trial[J]. JAMA Oncology, 9(1): 112-121. [42] Lim K H J, Schulz O, Lobon I, et al.2026. Cross-presentation of dead cell-associated antigens shapes the neoantigenic landscape of tumor immunity[J]. Nature Immunology, 27: 72-81. [43] Liu D, Tian J, Yu L, et al.2025. A modular metalloprotein in situ vaccine for cancer immunotherapy in mouse models of breast cancer[J]. Science Translational Medicine 17(782): eadk3269. [44] Liu Q, Chu Y H, Shao J, et al.2022. Benefits of an immunogenic personalized neoantigen nanovaccine in patients with high-risk gastric/gastroesophageal junction cancer[J]. Advanced Science (Weinh), 10(1): e2203298. [45] Luchner M, Reinke S, Milicic A.2021. TLR agonists as vaccine adjuvants targeting cancer and infectious diseases[J]. Pharmaceutics, 13(2): 142. [46] Ma L, Diao L, Peng Z, et al.2021. Immunotherapy and prevention of cancer by nanovaccines loaded with whole?cell components of tumor tissues or cells[J]. Advanced Materials, 33(43): 2104849. [47] Manspeaker M P, Thomas S N.2020. Lymphatic immunomodulation using engineered drug delivery systems for cancer immunotherapy[J]. Advanced Drug Delivery Reviews, 160: 19-35. [48] Marzolini N, Brysgel T V, Rahman R J, et al.2026. Targeting DNA-LNPs to endothelial cells improves expression magnitude, duration, and specificity[J]. Advanced Science, 13(14): e15480. [49] Matheu K C, Araya B C, Diaz F T, et al.2025. PLGA nanoencapsulation enhances immunogenicity of heat-shocked melanoma tumor cell lysates[J]. Cells, 14(24): 1939. [50] McKee A S, Marrack P.2017. Old and new adjuvants[J]. Current Opinion in Immunology, 47: 44-51. [51] Mendez-Gomez H R, Devries A, Castillo P, et al.2024. RNA aggregates harness the danger response for potent cancer immunotherapy[J]. Cell, 187(10): 2521-2535.e21. [52] Moni S S, Abdelwahab S I, Jabeen A, et al.2023. Advancements in vaccine adjuvants: The journey from alum to nano formulations[J]. Vaccines, 11(11): 1704. [53] Montaner-Tarbes S, Borras F E, Montoya M, et al.2016. Serum-derived exosomes from non-viremic animals previously exposed to the Porcine respiratory and reproductive virus contain antigenic viral proteins[J]. Veterinary Research, 47(1): 59. [54] Peng K, Zhao X X, Fu Y X, et al.2025. Eliciting antitumor immunity via therapeutic cancer vaccines[J]. Cellular & Molecular Immunology, 22: 840-868. [55] Peng S, Cao F Q, Xia Y F, et al.2020. Particulate alum via pickering emulsion for an enhanced COVID-19 vaccine adjuvant[J]. Advanced Materials, 32(40): e2004210. [56] Peruzzi D, Mesiti G, Ciliberto G, et al.2010. Telomerase and HER-2/neu as targets of genetic cancer vaccines in dogs[J]. Vaccine, 28(5): 1201-1208. [57] Roman F, Burny W, Ceregido M A, et al.2024. Adjuvant system AS01: From mode of action to effective vaccines[J]. Expert Review of Vaccines, 23(1): 715-729. [58] Rus Bakarurraini N A A, Ab Mutalib N S, Jamal R, et al.2020. The landscape of tumor-specific antigens in colorectal cancer[J]. Vaccines, 8(3): 371. [59] Schumacher T N, Scheper W, Kvistborg P.2019. Cancer neoantigens[J].Annual Review of Immunology, 37: 173-200. [60] Shen S, Gao Y, Ouyang Z, et al.2024. Photothermal-triggered dendrimer nanovaccines boost systemic antitumor immunity[J]. Journal of Controlled Release, 366: 114-125. [61] Shen S, Zhang Y, Chen K G, et al.2018. Cationic polymeric nanoparticle delivering CCR2 siRNA to inflammatory monocytes for tumor microenvironment modification and cancer therapy[J]. Molecular Pharmaceutics, 15(9): 3642-3653. [62] Shi Y W, Xu X Y, Liu X M, et al.2026. Nanovaccine based on glycocalyx-mimicking nanovehicle to potentiate the immunogenicity of neoantigen[J]. ACS Macro Letters, 15(1): 165-173. [63] Sun W W, Dai L L, Cao Y Q, et al.2023. Monocytes reprogrammed by tumor microparticle vaccine inhibit tumorigenesis and tumor development[J]. Cancer Nanotechnology, 14(1): 34. [64] Suwa T, Kobayashi M, Nam J M, et al.2021. Tumor microenvironment and radioresistance[J]. Experimental & Molecular Medicine, 53: 1029-1035. [65] Tang J, Meka A K, Theivendran S, et al.2020. Openwork@dendritic mesoporous silica nanoparticles for lactate depletion and tumor microenvironment regulation[J]. Angewandte Chemie International Edition, 59(49): 22054-22062. [66] Tang M Q, Guo Q H, Wang P, et al.2026. Marine bromophenol derivatives as a novel class of potent small-molecule STING agonists[J]. Current Issues in Molecular Biology, 48: 61. [67] Teng Z, Sun S, Luo X, et al.2021. Bi-functional gold nanocages enhance specific immunological responses of Foot-and-mouth disease virus-like particles vaccine as a carrier and adjuvant[J]. Nanomedicine: Nanotechnology, Biology, and Medicine, 33: 102358. [68] Vázquez-Maldonado N, Kelly H R, Leitner W W, et al.2023. Comprehensive immunoprofiling and systematic adjuvant comparisons for identifying suitable vaccine: Adjuvant pairings[J]. Human Vaccines & Immunotherapeutics, 19(2): 2223503. [69] Vedelago G, Palacios L M, Castell S D, et al.2025. Differential innate immune activation by four different CpG-ODNs in porcine and murine cells: Implications for vaccine design[J]. Research in Veterinary Science, 191: 105692. [70] Wang Y, Duan W, Yan C, et al.2026. STING signaling pathway: An oasis in the glioblastoma immune desert[J]. Theranostics, 16(7): 3384-3407. [71] Wang Y, Shan C, Ming S, et al.2009. Immunoadjuvant effects of bacterial genomic DNA and CpG oligodeoxynucleotides on Avian influenza virus subtype H5N1 inactivated oil emulsion vaccine in chicken[J]. Research in Veterinary Science, 86(3): 399-405. [72] Wei J J, Wu D, Zhao S S, et al.2022. Immunotherapy of malignant glioma by noninvasive administration of TLR9 agonist CpG nano-immunoadjuvant[J]. Advanced Science, 9(13): 2103689. [73] Wen L J, Peng Y, Wang K, et al.2022. Regulation of pathological BBB restoration via nanostructured ROS-responsive glycolipid-like copolymer entrapping siVEGF for glioblastoma targeted therapeutics[J]. Nano Research, 15: 1455-1465. [74] Yao M, Liu X Y, Qian Z B, et al.2023. Research progress of nanovaccine in anti-tumor immunotherapy[J]. Frontiers in Oncology, 13: 1211262. [75] Zaccariotto G C, Bistaffa M J, Zapata A M M, et al.2025. Cancer nanovaccines: Mechanisms, design principles, and clinical translation[J]. ACS Nano, 19: 16204-16223. [76] Zhang D D, Guo S Q Y, Yuan J, et al.2026. Toward next-generation therapeutic HPV vaccines: A review on expanding the antigen repertoire and an integrated bioinformatics selection framework[J]. Human Vaccines & Immunotherapeutics, 22(1): 2610899. [77] Zhang T, He P, Guo D, et al.2023. Research progress of aluminum phosphate adjuvants and their action mechanisms[J]. Pharmaceutics, 15(6): 1756. [78] Zhao C, Zhang Y, Bao X, et al.2026. Multicomponent nanoassembly integrating photosensitizer and astragalus polysaccharide adjuvant for amplified photoimmunotherapy via hypoxia adaptation disruption[J]. Nano Research. 19: 94908620. [79] Zhao Y, Baldin A V, Isayev O, et al.2021. Cancer vaccines: Antigen selection strategy[J]. Vaccines, 9(2): 85. [80] Zhu L, Han Z, He Y, et al.2022. Caspase-1-dependent pyroptosis mediates adjuvant activity of platycodin D as an adjuvant for intramuscular vaccines[J]. Cells, 11(1): 134. [81] Zou Y, Li S, Li Y, et al.2025. Glioblastoma cell derived exosomes as a potent vaccine platform targeting primary brain cancers and brain metastases[J]. ACS Nano, 19(18): 17309-17322.
