- Markets and Markets
- The Cell and Gene Therapy Catapult
- Gervois P.
- Wolfs E.
- Ratajczak J.
- Dillen Y.
- Vangansewinkel T.
- Hilkens P.
- et al.
- Hare J.M.
- Fishman J.E.
- Gerstenblith G.
- DiFede Velazquez D.L.
- Zambrano J.P.
- Suncion V.Y.
- et al.
|Adenovirus||Double-stranded DNA||DNA incorporated into host cell nucleus|
Infects dividing and quiescent cells
Transient gene expression
Lower risk of genotoxicity
Large DNA inserts
|Transient gene expression|
|Adeno-associated virus (AAV)||Single-stranded DNA||Infects dividing and quiescent cells|
Long-term gene expression
|Small DNA inserts|
|Retrovirus||Single-stranded RNA||DNA incorporated into host cell genome|
Long-term stable gene expression
|Lentivirus||Single-stranded RNA||DNA incorporated into host cell genome|
Long-term stable gene expression
Infects dividing and quiescent cells
No insertion into oncogene
Genetically engineered MSCs as cancer therapeutics
- Cancer Research UK
|Tumor type||Therapeutic modification||Cell type||Effects||Ref|
|Breast||IFN-β||BM-MSC||Reduced tumor growth and metastases and prolonged survival|
|Breast||TRAIL||BM-MSC||Reduced tumor growth and metastases|
|Lung||PEDF||mBM-MSC||Reduced tumor growth and prolonged survival|
|Lung||TRAIL||hUC-MSC||Prolonged survival and increased tumor apoptosis|
|Mesothelioma||TRAIL||hBM-MSC||Reduced tumor growth|
|Glioma||CDU||hAD-MSC||Tumor regression and prolonged survival|
|Glioma||HSV-tK||hAD-MSC||Reduced tumor growth|
|Glioma||TRAIL||hUC-MSC||Reduced tumor growth|
Irradiation enhances the tumor tropism and therapeutic potential of tumor necrosis factor-related apoptosis-inducing ligand-secreting human umbilical cord blood-derived mesenchymal stem cells in glioma therapy.
Stem Cells. 2010; 28: 2217-2228
|Glioma||TRAIL||hBM-MSC||Inhibits tumor growth|
|HCC||Apoptin||hBM-MSC||Reduced tumor volume|
|HCC||HNF4α||hUC-MSC||Reduced tumor growth|
|HCC||IFN-β||hBM-MSC||Decreased tumor formation|
|HCC||HSV-tK||mBM-MSC||Reduced tumor growth|
Selective targeting of genetically engineered mesenchymal stem cells to tumor stroma microenvironments using tissue-specific suicide gene expression suppresses growth of hepatocellular carcinoma.
Ann Surg. 2011; 254 (discussion 74-5): 767-774
|Pancreas||HSV-tK||mBM-MSC||Reduced tumor growth and metastases|
|Ascites||IL-12||mBM-MSC||Reduced ascites volume and prolonged survival|
|Lymphoma||IL-21||mBM-MSC||Delayed tumor development and prolonged survival|
|Prostate||IFN-β||hBM-MSC||Reduced tumor weight and prolonged survival|
- Zolochevska O.
- Yu G.
- Gimble J.M.
- Figueiredo M.L.
Therapies in clinical trials
TREAT-ME1 trial for gastrointestinal tumors
- Niess H.
- Bao Q.
- Conrad C.
- Zischek C.
- Notohamiprodjo M.
- Schwab F.
- et al.
Clinical trial design
TACTICAL trial for lung cancer
Clinical trial design
Cell manufacture and release
- Stem Cell Therapy Market by Treatment Mode (Autologous & Allogeneic).(Therapeutic Applications (CNS, CVS, GIT, Wound Healing, Musculoskeletal, Eye, & Immune System)—Regulatory Landscape, Pipeline Analysis & Global Forecasts to 2020. 2014)accessed 31.08.16)
- UK Clinical Trials Database 2016 Commentary.https://ct.catapult.org.uk/wp-content/uploads/2016/07/Clinical-trials-database-2016-commentary.pdf(accessed 31.08.16])Date: 2016
- Autologous hematopoetic stem cell transplantation for refractory crohn disease: a randomized clinical trial.JAMA. 2015; 314: 2524-2534
- A placebo-controlled, randomized trial of mesenchymal stem cells in COPD.Chest. 2013; 143: 1590-1598
- In vivo effects of mesenchymal stromal cells in two patients with severe acute respiratory distress syndrome.Stem Cells Transl Med. 2015; 4: 1199-1213
- Therapeutic potential of mesenchymal stromal cells for acute respiratory distress syndrome.Ann Am Thorac Soc. 2015; 12 (S54–7)
- Clinical outcomes of transplanted modified bone marrow-derived mesenchymal stem cells in stroke: a phase 1/2a study.Stroke. 2016; 47: 1817-1824
- Stem cell-based therapies for ischemic stroke: preclinical results and the potential of imaging-assisted evaluation of donor cell fate and mechanisms of brain regeneration.Med Res Rev. 2016; https://doi.org/10.1002/med.21400
- Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial.JAMA. 2012; 308: 2369-2379
- Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease.Circ Res. 2011; 109: 923-940
- Efficacy of mesenchymal stem cell therapy for steroid-refractory acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis.PLoS ONE. 2015; 10 (e0136991)
- Cartilage tissue engineering: what have we learned in practice?.Methods Mol Biol. 2015; 1340: 3-21
- The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells.Cell Tissue Kinet. 1970; 3: 393-403
- Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.Cytotherapy. 2006; 8: 315-317
- Repair of tissues by adult stem/progenitor cells (MSCs): controversies, myths, and changing paradigms.Mol Ther. 2009; 17: 939-946
- Bone marrow-derived mesenchymal stem cells: isolation, expansion, characterization, viral transduction, and production of conditioned medium.Methods Mol Biol. 2009; 482: 281-294
- Enzymatic and non-enzymatic isolation systems for adipose tissue-derived cells: current state of the art.Cell Regen (Lond). 2015; 4: 7
- Mesenchymal stromal cells from umbilical cord blood.Curr Stem Cell Res Ther. 2007; 2: 310-323
- Tumor tropism of mesenchymal stem cells.in: Shah K. Stem cell therapeutics for cancer. John Wiley & Sons, Inc, Hoboken, NJ2013
- MSC and tumors: homing, differentiation, and secretion influence therapeutic potential.Adv Biochem Eng Biotechnol. 2013; 130: 209-266
- Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas.Cancer Res. 2005; 65: 3307-3318
- Assessmentof therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy.Proc Natl Acad Sci USA. 2009; 106: 4822-4827
- Mesenchymal stem cell-mediated delivery of the sodium iodide symporter supports radionuclide imaging and treatment of breast cancer.Stem Cells. 2011; 29: 1149-1157
- Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells.Cancer Gene Ther. 2007; 14: 894-903
- Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer.Cancer Res. 2009; 69: 4134-4142
- Systemic but not topical TRAIL-expressing mesenchymal stem cells reduce tumour growth in malignant mesothelioma.Thorax. 2014; 69: 638-647
- Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo.Hepatology. 2008; 47: 1634-1643
- Human mesenchymal stem cells inhibit metastasis of a hepatocellular carcinoma model using the MHCC97-H cell line.Cancer Sci. 2010; 101: 2546-2553
- Radiation increases invasion of gene-modified mesenchymal stem cells into tumors.Int J Radiat Oncol Biol Phys. 2009; 75: 843-853
- Mesenchymal stromal cells alone or expressing interferon-beta suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment.Cytotherapy. 2010; 12: 615-625
- Targeting tumor stroma using engineered mesenchymal stem cells reduces the growth of pancreatic carcinoma.Ann Surg. 2009; 250: 747-753
- Mesenchymal stem cells as therapeutic delivery vehicles targeting tumor stroma.Cancer Biother Radiopharm. 2011; 26: 767-773
- Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors.Cancer Res. 2002; 62: 3603-3608
- Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma.J Exp Med. 2006; 203: 1235-1247
- Activation of signal transducers and activators of transcription 3 and focal adhesion kinase by stromal cell-derived factor 1 is required for migration of human mesenchymal stem cells in response to tumor cell-conditioned medium.Stem Cells. 2009; 27: 857-865
- Targeting of mesenchymal stem cells to ovarian tumors via an artificial receptor.J Ovarian Res. 2010; 3: 12
- Macrophage migration inhibitory factor-CXCR4 is the dominant chemotactic axis in human mesenchymal stem cell recruitment to tumors.J Immunol. 2015; 194: 3463-3474
- The stromal derived factor-1/CXCL12-CXC chemokine receptor 4 biological axis in non-small cell lung cancer metastases.Am J Respir Crit Care Med. 2003; 167: 1676-1686
- Anti-donor immune responses elicited by allogeneic mesenchymal stem cells: what have we learned so far?.Immunol Cell Biol. 2013; 91: 40-51
- Immunogenicity of allogeneic mesenchymal stem cells.J Cell Mol Med. 2012; 16: 2094-2103
- Immunomodulatory properties of mesenchymal stromal cells.Blood. 2007; 110: 3499-3506
- Chondrogenic differentiation increases antidonor immune response to allogeneic mesenchymal stem cell transplantation.Mol Ther. 2014; 22: 655-667
- Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair.Circulation. 2010; 122: 2419-2429
- The immunogenicity and immunomodulatory function of osteogenic cells differentiated from mesenchymal stem cells.J Immunol. 2006; 176: 2864-2871
- Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells.Stem Cell Res Ther. 2013; 4: 125
- Mesenchymal stem cells are injured by complement after their contact with serum.Blood. 2012; 120: 3436-3443
- Engineering mesenchymal stem cells for regenerative medicine and drug delivery.Methods. 2015; 84: 3-16
- Mesenchymal stem cells as therapeutic agents and potential targeted gene delivery vehicle for brain diseases.J Control Release. 2012; 162: 464-473
- Therapeutic cell carriers: a potential road to cure glioma.Expert Rev Neurother. 2014; 14: 651-660
- Electroporation for targeted gene transfer.Expert Opin Drug Deliv. 2005; 2: 255-268
- Gene transfer by electroporation.Mol Biotechnol. 1997; 7: 5-35
- Electroporation as a method for high-level nonviral gene transfer to the lung.Gene Ther. 2003; 10: 1608-1615
- Electroporation therapy of solid tumors.Crit Rev Ther Drug Carrier Syst. 1999; 16: 523-569
- Intravenous delivery of naked plasmid DNA for in vivo cytokine expression.Biochem Biophys Res Commun. 2001; 289: 1088-1092
- Rat liver-targeted naked plasmid DNA transfer by tail vein injection.Mol Biotechnol. 2004; 26: 165-172
- The magnetofection method: using magnetic force to enhance gene delivery.Biol Chem. 2003; 384: 737-747
- Hydrodynamic delivery of DNA.Methods Mol Biol. 2004; 245: 245-250
- Progress and prospects: naked DNA gene transfer and therapy.Gene Ther. 2003; 10: 453-458
- Cationic polymer based gene delivery systems.Pharm Res. 2000; 17: 113-126
- Cationic lipid-DNA complexes for gene therapy: understanding the relationship between complex structure and gene delivery pathways at the molecular level.Curr Med Chem. 2004; 11: 133-149
- Non-viral gene delivery systems.Curr Opin Biotechnol. 2002; 13: 128-131
- Cellular interactions of therapeutically delivered nanoparticles.Expert Opin Drug Deliv. 2011; 8: 141-151
- Human mesenchymal stem cells maintain transgene expression during expansion and differentiation.Mol Ther. 2001; 3: 857-866
- Human fetal mesenchymal stem cells as vehicles for gene delivery.Stem Cells. 2005; 23: 93-102
- Gene therapy of X-linked severe combined immunodeficiency.Methods Mol Biol. 2003; 215: 247-259
- A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency.N Engl J Med. 2003; 348: 255-256
- Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy.Science. 2009; 326: 818-823
- Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia.Nature. 2010; 467: 318-322
- Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome.Science. 2013; 341: 1233151
- Overexpression of CXCR4 in mesenchymal stem cells promotes migration, neuroprotection and angiogenesis in a rat model of stroke.J Neurol Sci. 2012; 316: 141-149
- Epidermal growth factor receptor-transfected bone marrow stromal cells exhibit enhanced migratory response and therapeutic potential against murine brain tumors.Cancer Gene Ther. 2005; 12: 757-768
- Antitumor effects of TRAIL-expressing mesenchymal stromal cells in a mouse xenograft model of human mesothelioma.Cancer Gene Ther. 2015; 22: 44-54
- Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents.J Natl Cancer Inst. 2004; 96: 1593-1603
- Cancer gene therapy using mesenchymal stem cells expressing interferon-beta in a mouse prostate cancer lung metastasis model.Gene Ther. 2008; 15: 1446-1453
- Prophylaxis against carcinogenesis in three kinds of unestablished tumor models via IL12-gene-engineered MSCs.Carcinogenesis. 2006; 27: 2434-2441
- A tumor-selective biotherapy with prolonged impact on established metastases based on cytokine gene-engineered MSCs.Mol Ther. 2008; 16: 749-756
- In vitro effect of adenovirus-mediated human Gamma Interferon gene transfer into human mesenchymal stem cells for chronic myelogenous leukemia.Hematol Oncol. 2006; 24: 151-158
- Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1.PLoS Med. 2007; 4 (e269)
- Implantation of mesenchymal stem cells overexpressing endothelial nitric oxide synthase improves right ventricular impairments caused by pulmonary hypertension.Circulation. 2006; 114 (I181–5)
- Vascular endothelial growth factor-expressing mesenchymal stem cell transplantation for the treatment of acute myocardial infarction.Arterioscler Thromb Vasc Biol. 2005; 25: 1168-1173
- Cancer Statistics for the UK.accessed 09.08.16)
- Neo-organoid of marrow mesenchymal stromal cells secreting interleukin-12 for breast cancer therapy.Cancer Res. 2008; 68: 4810-4818
- Anti-angiogenesis therapy based on the bone marrow-derived stromal cells genetically engineered to express sFlt-1 in mouse tumor model.BMC Cancer. 2008; 8: 306
- Pigment epithelial-derived factor and melanoma differentiation associated gene-7 cytokine gene therapies delivered by adipose-derived stromal/mesenchymal stem cells are effective in reducing prostate cancer cell growth.Stem Cells Dev. 2012; 21: 1112-1123
- Mesenchymal stem cells as a gene therapy carrier for treatment of fibrosarcoma.Cytotherapy. 2009; 11: 516-526
- c-Jun N-terminal kinase contributes to apoptotic synergy induced by tumor necrosis factor-related apoptosis-inducing ligand plus DNA damage in chemoresistant, p53 inactive mesothelioma cells.J Biol Chem. 2003; 278: 25461-25467
- Bid mediates apoptotic synergy between tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and DNA damage.J Biol Chem. 2005; 280: 12486-12493
- A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death.Science. 2004; 305: 1471-1474
- Stem cell implants for cancer therapy: TRAIL-expressing mesenchymal stem cells target cancer cells in situ.J Breast Cancer. 2012; 15: 273-282
- Adipose-derived mesenchymal stem cells as stable source of tumor necrosis factor-related apoptosis-inducing ligand delivery for cancer therapy.Cancer Res. 2010; 70: 3718-3729
- In vitro anti-myeloma activity of TRAIL-expressing adipose-derived mesenchymal stem cells.Br J Haematol. 2012; 157: 586-598
- Inhibitory effect of genetically engineered mesenchymal stem cells with Apoptin on hepatoma cells in vitro and in vivo.Mol Cell Biochem. 2016; 416: 193-203
- Human adipose tissue-derived mesenchymal stem cells expressing yeast cytosinedeaminase::uracil phosphoribosyltransferase inhibit intracerebral rat glioblastoma.Int J Cancer. 2012; 130: 2455-2463
- Glioblastoma therapy with cytotoxic mesenchymal stromal cells optimized by bioluminescence imaging of tumor and therapeutic cell response.PLoS ONE. 2012; 7 (e35148)
- Safety and antitumor activity of recombinant soluble Apo2 ligand.J Clin Invest. 1999; 104: 155-162
- Chemoprevention of cancer.CA Cancer J Clin. 2004; 54: 150-180
- Why do so many cancer patients fail to respond to interferon therapy?.J Interferon Cytokine Res. 1996; 16: 275-281
- Interferon levels in human pulmonary tumors are lower than plasma levels.J Biol Regul Homeost Agents. 1990; 4: 153-156
- Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial.Lancet Respir Med. 2015; 3: 24-32
- Cancer statistics, 2014.CA Cancer J Clin. 2014; 64: 9-29
- Hallmarks of cancer: the next generation.Cell. 2011; 144: 646-674
- Anti-cancer therapies targeting the tumor stroma.Cancer Immunol Immunother. 2008; 57: 1-17
- Selective targeting of genetically engineered mesenchymal stem cells to tumor stroma microenvironments using tissue-specific suicide gene expression suppresses growth of hepatocellular carcinoma.Ann Surg. 2011; 254 (discussion 74-5): 767-774
- Treatment of advanced gastrointestinal tumors with genetically modified autologous mesenchymal stromal cells (TREAT-ME1): study protocol of a phase I/II clinical trial.BMC Cancer. 2015; 15: 237
- Global cancer statistics.CA Cancer J Clin. 2011; 61: 69-90
- sCLC. Chemotherapy in non-small cell lung cancer; a meta-analysis using updated data on individual patients from 52 randomised clinical trials.BMJ. 1995; 311: 899-909
- Identification and characterization of a new member of the TNF family that induces apoptosis.Immunity. 1995; 3: 673-682
- Defining the risks of mesenchymal stromal cell therapy.Cytotherapy. 2010; 12: 576-578
- Cryopreservation of human mesenchymal stromal cells expressing TRAIL for human anti-cancer therapy.Cytotherapy. 2016; 18: 860-869
- International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials.Cytotherapy. 2016; 18: 151-159
- Labelling of human mesenchymal stem cells with indium-111 for SPECT imaging: effect on cell proliferation and differentiation.Eur J Nucl Med Mol Imaging. 2006; 33: 1171-1177
- 111In oxine labelled mesenchymal stem cell SPECT after intravenous administration in myocardial infarction.Nucl Med Commun. 2003; 24: 1149-1154
- Therapeutic potential of bone marrow-derived mesenchymal stem cells producing pigment epithelium-derived factor in lung carcinoma.Int J Mol Med. 2012; 30: 527-534
- Human umbilical cord mesenchymal stem cells delivering sTRAIL home to lung cancer mediated by MCP-1/CCR2 axis and exhibit antitumor effects.Tumor Biol. 2016; 37: 8425-8435
- Use of genetically engineered bone marrow-derived mesenchymal stem cells for glioma gene therapy.Int J Oncol. 2009; 35: 1265-1270
- Irradiation enhances the tumor tropism and therapeutic potential of tumor necrosis factor-related apoptosis-inducing ligand-secreting human umbilical cord blood-derived mesenchymal stem cells in glioma therapy.Stem Cells. 2010; 28: 2217-2228
- Overexpression of hepatocyte nuclear factor 4alpha in human mesenchymal stem cells suppresses hepatocellular carcinoma development through Wnt/beta-catenin signaling pathway downregulation.Cancer Biol Ther. 2016; 17: 558-565
- Interferon-beta gene-modified human bone marrow mesenchymal stem cells attenuate hepatocellular carcinoma through inhibiting AKT/FOXO3a pathway.Br J Cancer. 2013; 109: 1198-1205
- Mesenchymal stem cells genetically modified by lentivirus-mediated interleukin-12 inhibit malignant ascites in mice.Exp Ther Med. 2014; 8: 1330-1334
- IL-21-expressing mesenchymal stem cells prevent lethal B-Cell lymphoma through efficient delivery of IL-21, which redirects the immune system to target the tumor.Stem Cells Dev. 2015; 24: 2808-2821
- Mesenchymal stem cells modified to express interferon-beta inhibit the growth of prostate cancer in a mouse model.J Int Med Res. 2012; 40: 317-327
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