The complexity and heterogeneity of individual tumors have hindered the efficacy of existing therapeutic cancer vaccines, sparking intensive interest in the development of more effective vaccines. Herein, we introduce a cancer nanovaccine for reactive oxygen species-augmented metalloimmunotherapy in which FeAl-layered double hydroxide (LDH) is used as a delivery vehicle with dihydroartemisinin (DHA) as cargo. The LDH framework is acid-labile and can be degraded in the tumor microenvironment, releasing iron ions, aluminum ions, and DHA. The iron ions contribute to aggravated intratumoral oxidative stress injury by the synergistic Fenton reaction and DHA activation, causing apoptosis, ferroptosis, and immunogenic cell death in cancer cells. The subsequently released tumor-associated antigens with the aluminum adjuvant form a cancer nanovaccine to generate robust and long-term immune responses against cancer recurrence and metastasis. Moreover, Fe ion-enabled -weighted magnetic resonance imaging can facilitate real-time tumor therapy monitoring. This cancer-nanovaccine-mediated metalloimmunotherapy strategy has the potential for revolutionizing the precision immunotherapy landscape.
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http://dx.doi.org/10.1021/acsnano.3c11960 | DOI Listing |
Mol Biomed
January 2025
Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Cancer vaccines, crucial in the immunotherapeutic landscape, are bifurcated into preventive and therapeutic types, both integral to combating oncogenesis. Preventive cancer vaccines, like those against HPV and HBV, reduce the incidence of virus-associated cancers, while therapeutic cancer vaccines aim to activate dendritic cells and cytotoxic T lymphocytes for durable anti-tumor immunity. Recent advancements in vaccine platforms, such as synthetic peptides, mRNA, DNA, cellular, and nano-vaccines, have enhanced antigen presentation and immune activation.
View Article and Find Full Text PDFAdv Healthc Mater
December 2024
Department of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34141, Republic of Korea.
Although interest in peptide-based cancer vaccines has surged in the era of personalized immunotherapy enabled by the discovery of neoantigens, the effective generation of neoantigen-specific T cell responses has been limited. Here, a Brucella BP26 protein-based nanoparticle displaying the MHC class II-restricted melanoma neoantigen, M30, is reported for use as a therapeutic cancer vaccine. Genetic engineering of 10 tandem repeats of the M30 neoepitope to a BP26 monomer results in the self-assembled, neoantigen-displaying protein nanoparticles (BP26-M30 NPs).
View Article and Find Full Text PDFAdv Mater
December 2024
State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
B lymphocytes have emerged as an important immune-regulating target. Inoculation with tumor cell membrane-derived vaccines is a promising strategy to activate B cells, yet their efficiency is limited due to lack of costimulatory molecules. To amplify B cell responses against tumor, herein, a spatiotemporally-synchronized antigen-adjuvant integrated nanovaccine, termed as CM-CpG-aCD40, is constructed by conjugating the immune stimulative CpG oligonucleotide and the anti-CD40 antibody (aCD40) onto the membrane vesicles derived from triple negative breast cancer cells.
View Article and Find Full Text PDFJ Control Release
December 2024
School of Medical Technology, Beijing Institute of Technology, Beijing 100081, PR China. Electronic address:
Cancer vaccines have garnered considerable interest for cancer immunotherapy. However, their effectiveness is limited by inadequate proliferation, activation, and tumor infiltration of cytotoxic T lymphocytes (CTLs). Inspired by the potent immunostimulatory properties of viral components and the exposure of calreticulin during immunogenic cell death (ICD) triggered by viral infections; in this study, we describe cGAMP@vEVs, a virus-mimicking nanovaccine strategy by engineering tumor cell-derived extracellular vesicles through virus infection, which co-load both personalized and broad antigen repertoire as well as multiple immune adjuvants to potently elicit antitumor immunity.
View Article and Find Full Text PDFFront Pharmacol
November 2024
Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
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