Improved efficacy of therapeutic vaccination with dendritic cells pulsed with tumor cell lysate against hepatocellular carcinoma by introduction of 2 tandem repeats of microbial HSP70 peptide epitope 407–426 and OK-432

Ge, Chiyu; Xing, Yun; Wang, Qi; Xiao, Wen; Lu, Yue; Xiangbing, Hu; Gao, Ziyan; Xu, Maolei; Ma, Yanju; Cao, Ruihua; Liu, Jingjing

doi:10.1016/j.intimp.2011.10.001

Cited by 7 publications

(4 citation statements)

References 31 publications

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“…It has been reported that TNF-α can activate MAPK and PI3K signaling pathways via TNFR1, which improve the expression of cell surface molecules and the secretion of cytokines, so that DCs are induced to maturation [31]. In this study, we found the transfection only with Adenovirus could also enhance DC maturation and modulate cytokine production, which were consistent with other studies [32]–[35]. It is reported that this mechanism may be independent of transgene expression, but dependent on viral entry into the cell and/or translocation to the nuclei [36].…”

Section: Discussionsupporting

confidence: 91%

Recombinant Mammaglobin A Adenovirus-Infected Dendritic Cells Induce Mammaglobin A-Specific CD8+ Cytotoxic T Lymphocytes against Breast Cancer Cells In Vitro

Cui

Zhang

et al. 2013

PLoS ONE

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Mammaglobin A (MGBA) is a novel breast cancer-associated antigen almost exclusively over-expressed in primary and metastatic human breast cancers, making it a potential therapeutic target for breast cancer. The development of dendritic cell (DC)-induced tumor antigen specific CD8+ cytotoxic T lymphocytes (CTLs) may hold promise in cancer immunotherapy. In this study we constructed recombinant replication-defective adenoviral (Ad) vectors encoding MGBA and evaluated their ability to trigger anti-tumor immunity in vitro. DCs were isolated from the human peripheral blood monocyte cells (PBMCs) of two HLA-A33+ healthy female volunteers, and infected with adenovirus carrying MGBA cDNA (Ad-MGBA). After that, the Ad-MGBA-infected DCs were used to stimulate CD8+ CTLs in vitro and the latter was used for co-culture with breast cancer cell lines. The data revealed that infection with Ad-MGBA improved DC maturation and up-regulated the expression of co-stimulatory molecules and the secretion of interleukin-12 (IL-12), but down-regulated interleukin-10 (IL-10) secretion from DCs. Ad-MGBA-infected DC-stimulated CD8+CTLs displayed the highest cytotoxicity towards HLA-A33+/MGBA+ breast cancer MDA-MB-415 cells compared with other CD8+CTL populations, and compared with the cytotoxicity towards HLA-A33−/MGBA+ breast cancer HBL-100 cells and HLA-A33−/MGBA− breast cancer MDA-MB 231 cells. In addition, Ad-MGBA-infected DC-stimulated CD8+ CTLs showed a high level of IFNγ secretion when stimulated with HLA-A33+/MGBA+ breast cancer MDA-MB-415 cells, but not when stimulated with HLA-A33−/MGBA+ HBL-100 and HLA-A33−/MGBA−MDA-MB-231 cells. In addition, killing of CD8+CTLs against breast cancer was in a major histocompability complex (MHC)-limited pattern. Finally, the data also determined the importance of TNF-α in activating DCs and T cells. These data together suggest that MGBA recombinant adenovirus-infected DCs could induce specific anti-tumor immunity against MGBA+ breast cancers, which could provide a novel strategy in the immunotherapy of breast cancer.

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Section: Discussionsupporting

confidence: 91%

Recombinant Mammaglobin A Adenovirus-Infected Dendritic Cells Induce Mammaglobin A-Specific CD8+ Cytotoxic T Lymphocytes against Breast Cancer Cells In Vitro

Cui

Zhang

et al. 2013

PLoS ONE

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“…Since found in 1973, dendritic cells (DC) pulsed with tumor-associated antigens have been applied as a therapeutic vaccine to tumor patients and they elicited an antitumor immune response (6,7). In addition, DC loaded with tumor cell lysate (TCL), prepared by the artificial lysis of tumor cells, significantly inhibited tumor growth, increased the survival of tumor-born mice and strengthened antitumor cytotoxic activity (8)(9)(10). However, it was reported that the application of TCL-loaded DC only elicited weak T cell responses (9).…”

Section: Introductionmentioning

confidence: 99%

Nifuroxazide prompts antitumor immune response of TCL-loaded DC in mice with orthotopically-implanted hepatocarcinoma

et al. 2017

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Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with a poor prognosis and high mortality. At present, vaccination with tumor cell lysate (TCL) loaded dendritic cells (DC) has been shown to be an effective therapy against HCC. However, the ability of promoting the specific T cell immune response is rather weak, influencing the antitumor response. Thus, it is necessary to find a strategy to improve the antitumor effect of TCL-loaded DC. Activation of signal transducer and activator of transcription 3 (STAT3) significantly inhibits antitumor immune response and DC maturity. Nifuroxazide, an antidiarrheal agent, has been proved to directly inhibit STAT3 activation. Thus, we investigated whether nifuroxazide could improve the antitumor immune response in mice vaccinated with TCL-loaded DC. The study provides the theoretical and experimental basis for developing an effective adjuvant for DC vaccine to treat HCC. Our results showed that the administration of nifuroxazide and DC-loaded TCL could significantly improve the survival rate, inhibit the tumor growth, and prompt the antitumor immune responses in mice with orthotopically implanted hepatocarcinomas, thus, possibly providing a new combination strategy to treat HCC.

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“…MKT-077 disrupts the ATPase domain of HSP70 and impacts its function [111]. Another study evaluated the potential of HSP70 peptide vaccines as a therapeutic approach for HCC [112]. Overall, these findings suggest that HSP70 is a relevant therapeutic target for cancer.…”

Section: Hsp70 As a Therapeutic Targetmentioning

confidence: 99%

Functions and Therapeutic Use of Heat Shock Proteins in Hepatocellular Carcinoma

Paul,

Shreya,

Pandey

et al. 2024

Livers

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Heat shock proteins are intracellular proteins expressed in prokaryotes and eukaryotes that help protect the cell from stress. They play an important role in regulating cell cycle and cell death, work as molecular chaperons during the folding of newly synthesized proteins, and also in the degradation of misfolded proteins. They are not only produced under stress conditions like acidosis, energy depletion, and oxidative stress but are also continuously synthesized as a result of their housekeeping functions. There are different heat shock protein families based on their molecular weight, like HSP70, HSP90, HSP60, HSP27, HSP40, etc. Heat shock proteins are involved in many cancers, particularly hepatocellular carcinoma, the main primary tumor of the liver in adults. Their deregulations in hepatocellular carcinoma are associated with metastasis, angiogenesis, cell invasion, and cell proliferation and upregulated heat shock proteins can be used as either diagnostic or prognostic markers. Targeting heat shock proteins is a relevant strategy for the treatment of patients with liver cancer. In this review, we provide insights into heat shock proteins and heat shock protein-like proteins (clusterin) in the progression of hepatocellular carcinoma and their use as therapeutic targets.

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Improved efficacy of therapeutic vaccination with dendritic cells pulsed with tumor cell lysate against hepatocellular carcinoma by introduction of 2 tandem repeats of microbial HSP70 peptide epitope 407–426 and OK-432

Cited by 7 publications

References 31 publications

Recombinant Mammaglobin A Adenovirus-Infected Dendritic Cells Induce Mammaglobin A-Specific CD8+ Cytotoxic T Lymphocytes against Breast Cancer Cells In Vitro

Recombinant Mammaglobin A Adenovirus-Infected Dendritic Cells Induce Mammaglobin A-Specific CD8+ Cytotoxic T Lymphocytes against Breast Cancer Cells In Vitro

Nifuroxazide prompts antitumor immune response of TCL-loaded DC in mice with orthotopically-implanted hepatocarcinoma

Functions and Therapeutic Use of Heat Shock Proteins in Hepatocellular Carcinoma

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