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Immunotherapy and Immune Responses / Vaccines and Immunoinformatics Approaches · Journal article
The Journal of Immunology · July 28, 2026
Encouraging direction, but not yet definitive.
A Prime-Target neoantigen vaccination strategy combining subcutaneous priming and intra-tumor boosting with K3/c-di-AMP adjuvant suppressed tumor growth and prolonged survival in murine mesothelioma and pancreatic adenocarcinoma models. The strategy recruited neoantigen-specific CD4+ and CD8+ T cells into the tumor microenvironment and remodeled the immune landscape toward an effector phenotype, providing mechanistic evidence in cold tumor models.
Preclinical controlled in vivo study in murine tumor models. Murine cold tumors (mesothelioma AE17 and pancreatic adenocarcinoma KPC-4662 cell lines) resistant to immunotherapy. Intervention: Prime-Target neoantigen vaccination: subcutaneous priming followed by intra-tumor boosting with neopeptides and K3/c-di-AMP adjuvant. Compared with: Control groups receiving intra-tumor adjuvants alone or neopeptides alone after subcutaneous vaccination (implied from results text).
P/T vaccination markedly suppressed tumor growth and prolonged survival in murine cold tumor models Neither intra-tumor adjuvants nor neopeptides alone after subcutaneous vaccination confer protection P/T vaccination recruits massive novel TCR clones of neoantigen-specific CD4+ Th1 cells and effector CD8+ T cells into the tumor
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
This preclinical work provides a mechanistic rationale for Prime-Target neoantigen vaccination in cold tumors, but clinical translation requires confirmation in human trials. The approach may inform future neoantigen vaccine design targeting immunosuppressive solid tumors.
A sound preclinical study in murine cold tumor models showing mechanistic evidence of enhanced neoantigen-specific T cell immunity and tumor control, but limited to in vivo animal work without human clinical data.
As stated by the source record.
This preclinical work provides a mechanistic rationale for Prime-Target neoantigen vaccination in cold tumors, but clinical translation requires confirmation in human trials. The approach may inform future neoantigen vaccine design targeting immunosuppressive solid tumors.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
What is missing. This record has no reported figures. That is a gap in the analysis, not a judgement about the study.
Abstract Introduction Despite their great promise in cancer treatment, the clinical efficacy of therapeutic cancer vaccines against solid tumors remains limited because of the immunosuppressive cold tumor microenvironment (TME), which suppresses anti-tumor T-cell activity. To overcome this, we propose a novel “Prime-Target” neoantigen vaccination strategy (referred to as P/T vaccination) that combines subcutaneous (SQ) and intra-tumor (IT) neopeptide vaccinations with a potent adjuvant combination of K3 CpG plus c-di-AMP (K3/c-di-AMP). This strategy first primes systemic neopeptide-specific T cell responses and then targets cold tumors by recruiting neopeptide-specific T cells into TME. Methods Murine cold tumors that are resistant to immunotherapy such as mesothelioma (AE17) and pancreatic adenocarcinoma (KPC-4662) were vaccinated with SQ priming followed by IT boosting using corresponding neopeptides plus K3/c-di-AMP. Tumor growth and survival were assessed. Immune responses in the tumors were analyzed by flow cytometry and single-cell RNA/TCR sequencing. Results P/T vaccination markedly suppressed tumor growth and prolonged survival. These therapeutic effects require intratumoral delivery of the full neopeptide vaccine, as neither IT adjuvants nor neopeptides alone after SQ vaccination, confer protection. Mechanistically, P/T vaccination recruits massive novel TCR clones of neoantigen-specific CD4+ Th1 cells and effector CD8+ T cells into the tumor, while markedly increasing effector T cell/Treg ratios and reducing M2 macrophages within the TME. Conclusion The Prime-Target neoantigen vaccination elicits potent systemic anti-tumor T cell immunity and directs it to the tumor. This dramatically alters the TME, remodeling it towards an effector phenotype that is more favorable for tumor control. This novel approach provides a mechanistic framework for optimizing neoantigen vaccination strategies against immunosuppressive cold solid tumors. Funding Source the Department of Immunology of the Erasmus MC, the Dutch Cancer Society (KWF Grant 12837), International Joint Usage/Research Center, the Institute of Medical Science, the University of Tokyo (Project number K22-3063 and K25-3190) Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)
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