Personalized neoantigen-pulsed dendritic cell vaccines show superior immunogenicity to neoantigen-adjuvant vaccines in mouse tumor models

Zhang, Rui; Yuan, Fengjiao; Shu, Yang; Tian, Yaomei; Zhou, Bailing; Yi, Linglu; Zhang, Xueyan; Ding, Zhenyu; Xu, Hong‐Xi; Yang, Li

doi:10.1007/s00262-019-02448-z

Cited by 49 publications

(49 citation statements)

References 44 publications

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“… 23 , 24 Some studies reported that antigen-loaded DC vaccines induced stronger immune responses than vaccines composed of antigens and adjuvants. 25 , 26 Therefore, neoantigen-based DC vaccines for cancer treatment seem to be promising and have been extensively investigated. 24 To date, neoantigen-based DC vaccines have shown clinical success in melanoma and other solid tumors.…”

Section: Introductionmentioning

confidence: 99%

Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer

Ding

Zhang

et al. 2021

Sig Transduct Target Ther

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Neoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity. Dendritic cell (DCs) vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality. Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world. Despite the rapid development of targeted therapy and immune checkpoint inhibitors for lung cancer in recent years, their efficacy is still unsatisfactory overall. Therefore, there is an urgent unmet clinical need for lung cancer treatment. Here, we attempted to treat lung cancer using a personalized neoantigen peptide-pulsed autologous DC vaccine and conducted a single-arm, 2 medical centers, pilot study initiated by the investigator (ChiCTR-ONC-16009100, NCT02956551). The patients enrolled were patients with heavily treated metastatic lung cancer. Candidate neoantigens were derived from whole-exome sequencing and RNA sequencing of fresh biopsy tissues as well as bioinformatics analysis. A total of 12 patients were enrolled in this study. A total of 85 vaccine treatments were administered with a median value of 5 doses/person (range: 3–14 doses/person). In total, 12–30 peptide-based neoantigens were selected for each patient. All treatment-related adverse events were grade 1–2 and there were no delays in dosing due to toxic effects. The objective effectiveness rate was 25%; the disease control rate was 75%; the median progression-free survival was 5.5 months and the median overall survival was 7.9 months. This study provides new evidence for neoantigen vaccine therapy and new therapeutic opportunities for lung cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer

Ding

Zhang

et al. 2021

Sig Transduct Target Ther

Self Cite

160

112

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“…Neoantigens can be identified and selected using whole exome sequencing of tumor and blood cell DNA and bioinformatics algorithms. In a murine lung carcinoma model, neoantigen-pulsed DC vaccines were superior to neoantigen-adjuvant vaccines in activating immune responses and inhibiting tumor growth ( 101 ). A first demonstration of this approach in human subjects was provided in a phase 1 trial in metastatic melanoma, showing a remarkable induction of de novo T cell responses after vaccination with personalized tumor neoantigen-loaded DCs.…”

Section: The Way Forwardmentioning

confidence: 99%

Dendritic Cell-Based Immunotherapy in Lung Cancer

et al. 2021

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Lung cancer remains the leading cause of cancer-related death worldwide. The advent of immune checkpoint inhibitors has led to a paradigm shift in the treatment of metastatic non-small cell and small cell lung cancer. However, despite prolonged overall survival, only a minority of the patients derive clinical benefit from these treatments suggesting that the full anti-tumoral potential of the immune system is not being harnessed yet. One way to overcome this problem is to combine immune checkpoint blockade with different strategies aimed at inducing or restoring cellular immunity in a tumor-specific, robust, and durable way. Owing to their unique capacity to initiate and regulate T cell responses, dendritic cells have been extensively explored as tools for immunotherapy in many tumors, including lung cancer. In this review, we provide an update on the nearly twenty years of experience with dendritic cell-based immunotherapy in lung cancer. We summarize the main results from the early phase trials and give an overview of the future perspectives within this field.

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“…Same promising results were achieved in ovarian cancer patients by intranodal injection of neopeptide-loaded DC vaccine [ 36 ]. Interestingly, a recent study published by Zhang et al demonstrated that a personalized neoantigen-pulsed DC vaccine has superior immunogenicity to neoantigen-adjuvant vaccine in murine tumor models [ 37 ].…”

Section: Tumor-specific Antigensmentioning

confidence: 99%

Cancer Vaccines: Antigen Selection Strategy

et al. 2021

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Unlike traditional cancer therapies, cancer vaccines (CVs) harness a high specificity of the host’s immunity to kill tumor cells. CVs can train and bolster the patient’s immune system to recognize and eliminate malignant cells by enhancing immune cells’ identification of antigens expressed on cancer cells. Various features of antigens like immunogenicity and avidity influence the efficacy of CVs. Therefore, the choice and application of antigens play a critical role in establishing and developing CVs. Tumor-associated antigens (TAAs), a group of proteins expressed at elevated levels in tumor cells but lower levels in healthy normal cells, have been well-studied and developed in CVs. However, immunological tolerance, HLA restriction, and adverse events are major obstacles that threaten TAA-based CVs’ efficacy due to the “self-protein” characteristic of TAAs. As “abnormal proteins” that are completely absent from normal cells, tumor-specific antigens (TSAs) can trigger a robust immune response against tumor cells with high specificity and without going through central tolerance, contributing to cancer vaccine development feasibility. In this review, we focus on the unique features of TAAs and TSAs and their application in vaccines, summarizing their performance in preclinical and clinical trials.

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Personalized neoantigen-pulsed dendritic cell vaccines show superior immunogenicity to neoantigen-adjuvant vaccines in mouse tumor models

Cited by 49 publications

References 44 publications

Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer

Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer

Dendritic Cell-Based Immunotherapy in Lung Cancer

Cancer Vaccines: Antigen Selection Strategy

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