title: The development of a novel cancer immunotherapeutic platform using tumor-targeting mesenchymal stem cells and a protein vaccine.
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.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hon-Jian
authors.initials: HJ
authors.lastname: Wei
authors.forename: Alexander T H
authors.initials: AT
authors.lastname: Wu
authors.forename: Chung-Huei
authors.initials: CH
authors.lastname: Hsu
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Lin
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Cheng
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Su
authors.forename: Wen-Ta
authors.initials: WT
authors.lastname: Chiu
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Whang-Peng
authors.forename: Frank L
authors.initials: FL
authors.lastname: Douglas
authors.forename: Win-Ping
authors.initials: WP
authors.lastname: Deng
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000276:immunology; D000818:Animals; D017209:Apoptosis; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005098:Exotoxins / Q000235:genetics / Q000276:immunology; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005805:Genes, MHC Class I / Q000276:immunology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012513:Sarcoma, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D010446:Peptide Fragments; D012333:RNA, Messenger; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A