Abstract
An ideal anticancer strategy should target only the malignant cells but spare the normal ones. In this regard, we established a platform, consisting of an antigen-delivering vehicle and a protein vaccine, for developing an immunotherapeutic approach with the potential for eliminating various cancer types. Mesenchymal stem cells (MSCs) have been demonstrated capable of targeting tumors and integrating into the stroma. Moreover, we have developed a protein vaccine PE(ΔIII)-E7-KDEL3 which specifically recognized E7 antigen and elicited immunity against cervical cancer. Taking advantage of tumor-homing property of MSCs and PE(ΔIII)-E7-KDEL3, we used E6/E7-immortalized human MSCs (KP-hMSCs) as an E7 antigen-delivering vehicle to test if this protein vaccine could effectively eliminate non-E7-expressing tumor cells. Animals which received combined treatment of KP-hMSCs and PE(ΔIII)-E7-KDEL3 demonstrated a significant inhibition of tumor growth and lung-metastasis when compared to PE(ΔIII)-E7-KDEL3 only and KP-hMSCs only groups. The efficiency of tumor suppression correlated positively to the specific immune response induced by PE(ΔIII)-E7-KDEL3. In addition, this combined treatment inhibited tumor growth via inducing apoptosis. Our findings indicated that KP-hMSCs could be used as a tumor-targeting device and mediate antitumor effect of PE(ΔIII)-E7-KDEL3. We believe this strategy could serve as a platform for developing a universal vaccine for different cancer types.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP Ribose Transferases / genetics
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ADP Ribose Transferases / immunology
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Animals
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Apoptosis
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Bacterial Toxins / genetics
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Bacterial Toxins / immunology
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Blotting, Western
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CD8-Positive T-Lymphocytes / immunology
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Enzyme-Linked Immunosorbent Assay
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Exotoxins / genetics
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Exotoxins / immunology
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Female
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Fibrosarcoma / immunology
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Fibrosarcoma / pathology
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Fibrosarcoma / prevention & control*
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Genes, MHC Class I / immunology
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Humans
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Image Processing, Computer-Assisted
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Lung Neoplasms / immunology
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Lung Neoplasms / prevention & control*
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Lung Neoplasms / secondary
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Mesenchymal Stem Cells / cytology
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Mesenchymal Stem Cells / immunology*
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Mesenchymal Stem Cells / metabolism
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Mice
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Middle Aged
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Oncogene Proteins, Viral / genetics
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Papillomaviridae / genetics
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Papillomavirus E7 Proteins / genetics
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Papillomavirus E7 Proteins / immunology*
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Papillomavirus Infections / immunology
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Papillomavirus Infections / pathology
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Papillomavirus Infections / prevention & control*
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Papillomavirus Vaccines / therapeutic use*
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Peptide Fragments / metabolism
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Pseudomonas aeruginosa Exotoxin A
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Sarcoma, Experimental / immunology
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Sarcoma, Experimental / pathology
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Sarcoma, Experimental / prevention & control*
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T-Lymphocytes, Cytotoxic / immunology
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Virulence Factors / genetics
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Virulence Factors / immunology
Substances
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Bacterial Toxins
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Exotoxins
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Oncogene Proteins, Viral
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Papillomavirus E7 Proteins
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Papillomavirus Vaccines
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Peptide Fragments
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RNA, Messenger
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Virulence Factors
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ADP Ribose Transferases