Therapeutic potential of human mesenchymal stem cells producing IL-12 in a mouse xenograft model of renal cell carcinoma

Gao, Peng; Ding, Qiang; Wu, Zhong; Jiang, Haowen; Fang, Zhaoxi

doi:10.1016/j.canlet.2009.08.031

Cited by 131 publications

(83 citation statements)

References 34 publications

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“…Two unique properties of MSCs provide them advantages over other cellular delivery vehicles, especially in the metastatic setting: (i) tumor tropic capabilities of MSCs enable target-specific delivery of therapeutic agents (8), which can be especially beneficial when surgical resection is not indicated because of the metastatic dissemination of cancer cells to other organs, and (ii) hypoimmunogenic properties of MSCs allow sustained release of therapeutic molecules without eliciting unwanted immune response, even in the allogeneic or xenogeneic settings (9). The efficacy and safety of MSCs as delivery vehicles were shown in preclinical models of RCC, in which human bone marrow-derived MSCs transduced with adenovirus encoding IL-12 (10) or those loaded with conditionally replicative oncolytic adenovirus (11) were used to generate tumor site-specific antitumor effects in subcutaneous and orthotopic xenograft models, respectively.…”

Section: Introductionmentioning

confidence: 99%

Complete Regression of Metastatic Renal Cell Carcinoma by Multiple Injections of Engineered Mesenchymal Stem Cells Expressing Dodecameric TRAIL and HSV-TK

Kim

Park

et al. 2013

Clinical Cancer Research

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Purpose: Durable complete remission of metastatic renal cell carcinoma (RCC) has rarely been achieved with current treatment modalities. To solve this problem, alternative therapeutic options with high efficacy and minimal side effects are strongly needed.Experimental Design: Mesenchymal stem cells (MSC) were engineered to coexpress dodecameric TRAIL and herpes simplex virus thymidine kinase (MSC/dTRAIL-TK). The antitumor effects of MSCs expressing dTRAIL (MSC/dTRAIL) or HSV-TK alone (MSC/TK) and MSC/dTRAIL-TK were compared with murine RCC cells using in vitro coculture system and in vivo experimental lung metastasis model. The effects of different doses and schedules of engineered MSCs on mice survival were also evaluated.Results: MSC/dTRAIL-TK exerted stronger apoptotic response in Renca cells than did MSC/TK or MSC/ dTRAIL after ganciclovir (GCV) treatment. In vivo imaging results suggest that MSCs reside longer in the lungs of metastatic tumor-bearing mice, compared with that of control mice, regardless of genetic engineering. In addition, MSC/dTRAIL-TK treatment followed by ganciclovir administrations significantly decreased the number of tumor nodules in the lung, to a greater degree than MSC/dTRAIL or MSC/TK, and led to a prolonged survival. More importantly, the antimetastatic effect of MSC/dTRAIL-TK was markedly enhanced by repeated injections but not by increased dose, and resulted in 100% survival of tumor-bearing mice after three injections.Conclusion: Sequential combination gene therapy using MSC/dTRAIL-TK achieved long-term remission of metastatic RCC without noticeable toxicity. Our findings provide an innovative therapeutic approach to completely eradicate metastatic tumors by simple, repeated administrations of MSC/dTRAIL-TK.

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Section: Introductionmentioning

confidence: 99%

Complete Regression of Metastatic Renal Cell Carcinoma by Multiple Injections of Engineered Mesenchymal Stem Cells Expressing Dodecameric TRAIL and HSV-TK

Kim

Park

et al. 2013

Clinical Cancer Research

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“…The underlying principle is that the immunosuppressive cancer location can be changed into one that makes the immune action, not in favour of cancer [167]. Some of the human MSCs have made for the release of IL-12 or IL-18 and they have been experienced in mice having carcinoma of renal cell, cervical tumor and glioblastoma [168][169][170][171][172]. All of these researches to cancer and stem cells inter-related continued company of ILs released by SC along with transfers in immune profile, involving high concentrations of IFNγ, establishment of natural, healthy killer cells and employment of tumor-specific T cells, thus leads to prolonged existence and the estimation of proceeds.…”

Section: Development Of Anticancer Stem Cellsmentioning

confidence: 99%

Development of Anti-Cancer Stem Cells as Theranostic Agents in the Treatment of Different Cancer Types: An Update

Malik¹,

Rasool²,

Khan³

et al. 2017

J Carcinog Mutagen

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Various unprecedented anti-tumor potential targets that robustly target cancer cells while sparing normal cells have been produced by biomedical research in cancer therapeutic intervention for interrupting disease progression and their cure. Stem cells characterize an accessible cell source for novel cell based clinical therapies by inhibiting tumor progression signalling pathways. They carry distinctive characteristics of isolation and migration to tissue inflammation site, inherited modifiability and protein expression. Stem cells are also used in immune-reconstitution and tissue regeneration. Implication of different types of stem cells as an attractive candidate for targeted delivery of anti-neoplastic agents has emerged as a promising field in anticancer therapy. Mutual interaction between cancer cells and stem cells results in effective and safer clinical therapy for tumors. Keeping in view, this review highlights the potential role of stem cells in the progression of tumor metastasis and also summarizes the role of different signaling pathways in carcinogenesis and their involvement in disease treatment. It also focuses on the current advances in stem cells practice in therapeutics of cancer.

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“…Stem cells are also utilized to delivery immunestimulatory cytokines including IL-12 (Duan et al, 2009;Eliopoulos et al, 2008;Gao et al, 2010), IL-21 (Hu et al, 2011), IL-24 , TNF-α (Shahrokhi et al, 2013), and IFN-γ (Bitsika et al, 2012). TRAIL (tumor necrosis factor related apoptosis induced ligand) (Shahrokhi et al, 2013) , nanoparticles (Gao et al, 2013) and anti-angiogenic factors (Ghaedi et al, 2011).…”

Section: Stem Cells As Vectors Carrying Therapeutic Reagents To Tumorsmentioning

confidence: 99%

Stem cell technology and engineering for cancer treatment

Truong

Pham

2015

Biomed Res Ther

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Abstract-Stem cells are not only widely used for regenerative medicine, but are also considered as a useful tool for cancer treatment. For a long time, stem cells have been utilized to renew the immune system for radiation or chemotherapy treated patients. Recently, stem cells are being engineered to carry therapeutic reagents to target tumor sites. Cancer vaccines based on the knowledge of cancer stem cells have been studied and applied for cancer treatment. Induced pluripotent stem cells have been used to create active T cells to support cancer immunotherapy. Those are due to the unique characteristics of stem cells, such as immunological tolerance, migration, and tissue reparation. This review discusses stem cell applications in transplantation, stem cell-based carriers, induced-pluripotent stem cells, cancer stem cells, and potential of stem cells engineering to revolutionize cancer treatment.

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Therapeutic potential of human mesenchymal stem cells producing IL-12 in a mouse xenograft model of renal cell carcinoma

Cited by 131 publications

References 34 publications

Complete Regression of Metastatic Renal Cell Carcinoma by Multiple Injections of Engineered Mesenchymal Stem Cells Expressing Dodecameric TRAIL and HSV-TK

Complete Regression of Metastatic Renal Cell Carcinoma by Multiple Injections of Engineered Mesenchymal Stem Cells Expressing Dodecameric TRAIL and HSV-TK

Development of Anti-Cancer Stem Cells as Theranostic Agents in the Treatment of Different Cancer Types: An Update

Stem cell technology and engineering for cancer treatment

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