The development of a novel cancer immunotherapeutic platform using tumor-targeting mesenchymal stem cells and a protein vaccine
Journal
Molecular Therapy
Journal Volume
19
Journal Issue
12
Pages
2249-2257
Date Issued
2011
Author(s)
Wei H.-J.
Wu A.T.
Hsu C.-H.
Lin Y.-P.
Su C.-H.
Chiu W.-T.
Whang-Peng J.
Douglas F.L.
Deng W.-P.
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. ? The American Society of Gene & Cell Therapy.
SDGs
Other Subjects
cancer vaccine; PE(deltaIII) E7 KDEL3 vaccine; protein E7; unclassified drug; animal cell; animal experiment; animal model; animal tissue; apoptosis; article; cancer cell culture; cancer immunization; cancer immunotherapy; cancer inhibition; cell homing; cell immortalization; controlled study; drug efficacy; female; fibrosarcoma; human; human cell; immune response; lung metastasis; mesenchymal stem cell; mouse; nonhuman; tumor immunity; tumor regression; tumor xenograft; uterine cervix cancer; Animalia
Type
journal article