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MTBHsp70-exFPR1-pulsed Dendritic Cells Enhance the Immune Response against Cervical Cancer.

ABSTRACT: Cervical cancer is the most common malignancy of the female reproductive system. Dendritic cell (DC)-based immunological therapy is a novel treatment for this cancer. DCs are specialized antigen-presenting cells (APCs) in the human immune system, and they can activate the T cells used in tumor immunological therapy. In this study, we developed a novel immunotherapeutic peptide by linking the Mycobacterium tuberculosis (MTB) heat shock protein 70 (Hsp70) functional peptide to the extracellular domain of FPR1, a protein overexpressed in cervical cancer, to obtain an MTBHsp70-exFPR1 fusion protein. Our experiments confirmed that the MTBHsp70-exFPR1 protein could promote DC maturation and induce the secretion of IL-12p70, IL-1?, and TNF-?. The antitumor effect of human cytotoxic T lymphocytes (CTLs) activated by autologous DCs was assessed in NOG mice. These results indicate that DCs pulsed with MTBHsp70-exFPR1 can enhance antitumor immunity against cervical cancer, providing a novel immune therapeutic strategy.

SUBMITTER: Cao G

PROVIDER: S-EPMC6856742 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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MTBHsp70-exFPR1-pulsed Dendritic Cells Enhance the Immune Response against Cervical Cancer.

Cao Guangming G Cui Ran R Liu Chongdong C Zhang Guyu G Zhang Zhenyu Z

Journal of Cancer 20191019 25

Cervical cancer is the most common malignancy of the female reproductive system. Dendritic cell (DC)-based immunological therapy is a novel treatment for this cancer. DCs are specialized antigen-presenting cells (APCs) in the human immune system, and they can activate the T cells used in tumor immunological therapy. In this study, we developed a novel immunotherapeutic peptide by linking the <i>Mycobacterium tuberculosis</i> (MTB) heat shock protein 70 (Hsp70) functional peptide to the extracell ...[more]

PMID: 31772669

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Project description:ObjectiveDendritic cells (DCs) are administered as immunotherapeutic adjuvants after the completion of standard treatment in most settings. However, our Phase I trial indicated that one patient out of four, who received autologous tumor lysate-pulsed dendritic cell (TLDC) also received cisplatin chemotherapy and experienced complete regression of her lung lesion, continuing to be disease free till date. Hence, the objective of our current study is to evaluate the sustenance or augmentation of immune responses when autologous human papillomavirus positive cervical tumor lysate pulsed DC- are combined with cisplatin, using co-culture assays in vitro.MethodsBefore treatment, peripheral blood and punch biopsy samples were collected from 23 cervical cancer patients after obtaining an informed consent. DC functionality was confirmed through phenotypic and functional assays using autologous peripheral blood mononuclear cells as responders. For cisplatin experiments, the drug was added at 150, 200 (clinical dose equivalent), and 400 μM concentrations to DCs alone or DC-T cell co-cultures. Phenotypic assessment and functional characterization of DCs was done using flow cytometry. Cytokine enzyme-linked immunosorbent assay and interferon (IFN)-γ enzyme-linked immune absorbent spot assays were also performed.ResultsThe functionality of TLDCs was not compromised upon cisplatin treatment in vitro even at the highest (400 μM) concentration. Even though cisplatin treatment reduced the secretion of IFN-γ and interleukin (IL)-12p40 in co-cultures stimulated with TLDCs, this effect was not significant (p>0.05). A doubling of IFN-γ secretion following cisplatin treatment was observed in at least one of three independent experiments. Additional experiments showed a reduction in both FOXP3+ regulatory T cells and IL-10 levels.ConclusionOur results provide evidence that cisplatin treatment may be given after autologous TLDC administration to maintain or improve a productive anti-tumor response in vaccinated patients.

Dataset Information

MTBHsp70-exFPR1-pulsed Dendritic Cells Enhance the Immune Response against Cervical Cancer.

Publications

MTBHsp70-exFPR1-pulsed Dendritic Cells Enhance the Immune Response against Cervical Cancer.

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