Despite the success of immune checkpoint inhibitors in revolutionizing oncology, their benefits remain limited to a small fraction of patients. Many tumors develop resistance or evade immune detection through genetic and microenvironmental complexity. Neoantigens—unique proteins arising from cancer-specific mutations—have emerged as ideal targets for immune attack because they exist only on tumor cells. When these antigens are presented by dendritic cells (DCs), the body can mount a precise and powerful response against malignancies. However, challenges such as identifying the right neoantigens, optimizing vaccine delivery, and preventing immune escape remain significant. Due to these challenges, researchers are now focusing on DC vaccines that harness patient-specific neoantigens to achieve stronger and more sustained cancer immunity.
A research team from the Chinese PLA General Hospital has published (DOI: 10.20892/j.issn.2095-3941.2025.0267) a comprehensive review in Cancer Biology & Medicine (online September 29, 2025). The study highlights global clinical progress in using neoantigens-loaded DC vaccines. By summarizing results from multiple trials, the authors reveal how these vaccines—combining precise genetic targeting with the body’s innate immune intelligence—could become a new cornerstone in personalized immunotherapy for solid tumors.
Neoantigen-based DC vaccines represent a marriage of genomics and immunology. Researchers begin by sequencing a patient’s tumor DNA and RNA to identify mutations that produce novel antigens unseen by the immune system. These antigens can be produced as synthetic peptides or delivered as mRNA molecules encoding the same tumor-specific mutations. They are then loaded onto DCs—key immune sentinels that can activate T cells to recognize cancer cells. Once reintroduced into the patient, these armed DCs travel to lymph nodes, where they activate cytotoxic T cells to seek out and eliminate tumor cells. Clinical trials have already demonstrated encouraging outcomes. In hepatocellular carcinoma, the Neo-DCVac-02 vaccine delayed recurrence and achieved an 84.6% one-year recurrence-free survival rate. In advanced lung cancer, patients receiving Neo-DCVac achieved a 25% objective response rate with only mild side effects. Other studies involving whole-tumor-lysate and mRNA-loaded DC vaccines have further confirmed strong immune activation and prolonged disease control, especially when combined with checkpoint inhibitors such as nivolumab. Together, these findings highlight a new route to sustained antitumor immunity—training the immune system to remember and adapt to each patient’s unique cancer signature.
“DCs are nature’s most powerful messengers—they teach T cells how to recognize what doesn’t belong,” said Dr. Jianming Xu, corresponding author of the study. “By loading them with a patient’s own tumor-specific neoantigens, we can design vaccines that are as unique as the cancer itself. This personalized approach avoids harming normal tissue, stimulates long-term immune memory, and offers hope for patients whose tumors no longer respond to standard therapies. It’s a step toward truly individualized cancer medicine.”
Looking ahead, neoantigen-based DC vaccines may reshape how solid tumors are treated. Future strategies will likely integrate them with checkpoint inhibitors, chemotherapy, or adoptive T-cell therapy to enhance overall immune activation. Researchers also see great promise in administering these vaccines early—after surgery or ablation—to eliminate residual cancer cells and establish lasting protection. As sequencing, bioinformatics, and manufacturing technologies mature, large-scale clinical trials are expected to confirm their survival benefits. Ultimately, these personalized vaccines could transform cancer care, shifting the focus from generalized treatment to a new paradigm: teaching every patient’s immune system to remember—and permanently fight—their own cancer.
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References
DOI
10.20892/j.issn.2095-3941.2025.0267
Original Source URL
https://doi.org/10.20892/j.issn.2095-3941.2025.0267
About Cancer Biology & Medicine
Cancer Biology & Medicine (CBM) is a peer-reviewed open-access journal sponsored by China Anti-cancer Association (CACA) and Tianjin Medical University Cancer Institute & Hospital. The journal monthly provides innovative and significant information on biological basis of cancer, cancer microenvironment, translational cancer research, and all aspects of clinical cancer research. The journal also publishes significant perspectives on indigenous cancer types in China. The journal is indexed in SCOPUS, MEDLINE and SCI (IF 8.4, 5-year IF 6.7), with all full texts freely visible to clinicians and researchers all over the world (http://www.ncbi.nlm.nih.gov/pmc/journals/2000/).