Next-Generation Cancer Nanovaccines: Reprogramming the Tumor Microenvironment from Rational Design Toward Clinical Translation.
- 1Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
- 2Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, 528400, People's Republic of China.
- 3Nanomedicine Innovation Center Erasmus (NICE), Erasmus MC Cancer Institute, Rotterdam, 3015 GD, the Netherlands.
Abstract
Cancer vaccines have emerged as a promising immunotherapeutic strategy for inducing durable and tumour-specific immune responses; however, their clinical efficacy remains limited by poor antigen immunogenicity, inefficient delivery, tumor heterogeneity, and the highly immunosuppressive tumor microenvironment (TME). Recent advances in nanotechnology have expanded opportunities for the rational engineering of multifunctional nanoparticle (NP) platforms that can protect therapeutic cargo, enhance antigen presentation and lymphatic transport, co-deliver immunostimulatory adjuvants, and potentially improve immune modulation while reducing systemic exposure. This narrative review provides an overview of next-generation cancer nanovaccines, including lipid-, polymer-, peptide-, inorganic-, biomimetic-, theranostic, in situ-, and stimuli-responsive platforms, with emphasis on their physicochemical design principles, mechanisms of immune activation, and interactions with the TME. Particular attention is given to strategies targeting tumor -associated macrophages, myeloid-derived suppressor cells, regulatory T cells, cancer-associated fibroblasts, and tumor cells to support dendritic-cell maturation, cytotoxic T-cell activation, and anti-tumor immunity. Emerging personalized approaches, including neoantigen- and autologous cell-based nanovaccines, mRNA vaccine platforms, and combinations with immune checkpoint inhibitors, are also discussed. In addition, we examine the growing role of artificial intelligence, machine learning, and computational immunology in neoantigen prioritization, nanoparticle formulation optimization, immunogenicity prediction, and patient-specific vaccine design. Despite encouraging preclinical findings, most cancer nanovaccine platforms remain at the preclinical or early clinical stage, and translation is limited by tumor heterogeneity, variable immune responses, long-term safety and biodistribution concerns, manufacturing reproducibility, scale-up, and regulatory requirements. Overall, the integration of nanotechnology, immunology, precision medicine, and AI offers considerable potential to advance personalized cancer vaccination, but broader clinical validation and standardized manufacturing and evaluation frameworks are required before these platforms can achieve routine clinical application.
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BibTeX
@article{tabibzadeh2026nextgeneration,
title = {{Next-Generation Cancer Nanovaccines: Reprogramming the Tumor Microenvironment from Rational Design Toward Clinical Translation.}},
author = {Sarvin Tabibzadeh and Fansu Meng and Vahid Asghariazar and Elham Safarzadeh and Ali Esmaeili and Timo L M Ten Hagen and Leila Farhoudi and Yu Cai},
journal = {International journal of nanomedicine},
year = {2026},
month = nov,
doi = {10.2147/ijn.s645776},
url = {https://europepmc.org/article/MED/42999844},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Next-Generation Cancer Nanovaccines: Reprogramming the Tumor Microenvironment from Rational Design Toward Clinical Translation.
AU - Sarvin Tabibzadeh
AU - Fansu Meng
AU - Vahid Asghariazar
AU - Elham Safarzadeh
AU - Ali Esmaeili
AU - Timo L M Ten Hagen
AU - Leila Farhoudi
AU - Yu Cai
PY - 2026
DA - 2026/11/03
JO - International journal of nanomedicine
DO - 10.2147/ijn.s645776
UR - https://europepmc.org/article/MED/42999844
AB - Cancer vaccines have emerged as a promising immunotherapeutic strategy for inducing durable and tumour-specific immune responses; however, their clinical efficacy remains limited by poor antigen immunogenicity, inefficient delivery, tumor heterogeneity, and the highly immunosuppressive tumor microenvironment (TME). Recent advances in nanotechnology have expanded opportunities for the rational engineering of multifunctional nanoparticle (NP) platforms that can protect therapeutic cargo, enhance antigen presentation and lymphatic transport, co-deliver immunostimulatory adjuvants, and potentially improve immune modulation while reducing systemic exposure. This narrative review provides an overview of next-generation cancer nanovaccines, including lipid-, polymer-, peptide-, inorganic-, biomimetic-, theranostic, in situ-, and stimuli-responsive platforms, with emphasis on their physicochemical design principles, mechanisms of immune activation, and interactions with the TME. Particular attention is given to strategies targeting tumor -associated macrophages, myeloid-derived suppressor cells, regulatory T cells, cancer-associated fibroblasts, and tumor cells to support dendritic-cell maturation, cytotoxic T-cell activation, and anti-tumor immunity. Emerging personalized approaches, including neoantigen- and autologous cell-based nanovaccines, mRNA vaccine platforms, and combinations with immune checkpoint inhibitors, are also discussed. In addition, we examine the growing role of artificial intelligence, machine learning, and computational immunology in neoantigen prioritization, nanoparticle formulation optimization, immunogenicity prediction, and patient-specific vaccine design. Despite encouraging preclinical findings, most cancer nanovaccine platforms remain at the preclinical or early clinical stage, and translation is limited by tumor heterogeneity, variable immune responses, long-term safety and biodistribution concerns, manufacturing reproducibility, scale-up, and regulatory requirements. Overall, the integration of nanotechnology, immunology, precision medicine, and AI offers considerable potential to advance personalized cancer vaccination, but broader clinical validation and standardized manufacturing and evaluation frameworks are required before these platforms can achieve routine clinical application.
SN - 1176-9114
SN - 1178-2013
ER -