Stem and progenitor cell-mediated tumor selective gene therapy

Aboody, Karen S.; Najbauer, Joseph; Danks, Mary K.

doi:10.1038/gt.2008.41

Cited by 251 publications

(250 citation statements)

References 133 publications

(140 reference statements)

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“…18 However, incorporation into the tumor microenvironment is not always apparent. What is more, the role of recruited MSC in the tumor microenvironment remains unclear, given that recent evidence also suggests that they could have a role in tumor growth and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Factory neovessels: engineered human blood vessels secreting therapeutic proteins as a new drug delivery system

et al. 2010

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Several works have shown the feasibility of engineering functional blood vessels in vivo using human endothelial cells (ECs). Going further, we explored the therapeutic potential of neovessels after gene-modifying the ECs for the secretion of a therapeutic protein. Given that these vessels are connected with the host vascular bed, we hypothesized that systemic release of the expressed protein is immediate. As a proof of principle, we used primary human ECs transduced with a lentiviral vector for the expression of a recombinant bispecific aCEA/aCD3 antibody. These ECs, along with mesenchymal stem cells as a source of mural cells, were embedded in Matrigel and subcutaneously implanted in nude mice. High antibody levels were detected in plasma for 1 month. Furthermore, the antibody exerted a therapeutic effect in mice bearing distant carcinoembryonic-antigen (CEA)-positive tumors after inoculation of human T cells. In summary, we show for the first time the therapeutic effect of a protein locally secreted by engineered human neovessels.

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Section: Discussionmentioning

confidence: 99%

Factory neovessels: engineered human blood vessels secreting therapeutic proteins as a new drug delivery system

et al. 2010

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“…These immortalized cells show strong, directed migration toward primary brain tumors over large distances and can even track-down single, scattered glioblastoma cells. Hence, they are now considered as a cell-based delivery system for glioblastoma therapeutics (Aboody et al, 2008). However, the attraction of NPCs to CNS neoplasms is a phenomenon that is not restricted to exogenous NPCs, but also occurs endogenously in the brain.…”

Section: The Interaction Of Glioblastomas With Neural Precursor Cellsmentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

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687

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High-grade brain tumors are heterogeneous with respect to the composition of bona fide tumor cells and with respect to a range of intermingling parenchymal cells. Glioblastomas harbor multiple cell types, some with increased tumorigenicity and stem cell-like capacity. The stem-like cells may be the cells of origin for tumor relapse. However, the tumor-associated parenchymal cells such as vascular cells, microglia, peripheral immune cells, and neural precursor cells also play a vital role in controlling the course of pathology. In this review, we describe the multiple interactions of bulk glioma cells and glioma stem cells with parenchymal cell populations and highlight the pathological impact as well as signaling pathways known for these types of cell-cell communication. The tumor-vasculature not only nourishes glioblastomas, but also provides a specialized niche for these stem-like cells. In addition, microglial cells, which can contribute up to 30% of a brain tumor mass, play a role in glioblastoma cell invasion. Moreover, non-neoplastic astrocytes can be converted into a reactive phenotype by the glioma microenvironment and can then secrete a number of factors which influences tumor biology. The young brain may have the capacity to inhibit gliomagenesis by the endogenous neural precursor cells, which secrete tumor suppressive factors. The factors, pathways, and interactions described in this review provide a new prospective on the cell biology of primary brain tumors, which may ultimately generate new treatment modalities. However, our picture of the multiple interactions between parenchymal and tumor cells is still incomplete. V

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“…Targeting cancer stem cells, cancer stem cells are of particular interest in the literature, for their ability in initiation and maintenance of tumor growth and their potential role in early relapses and resistance to current therapies (Reya et al, 2001;Heppner, 1984;Al-Hajj et al, 2003;Clarke et al, 2006;Massard et al, 2006;Dwyer et al, 2007;Aboody et al, 2008;Nakshatri, 2010;Bohl et al, 2011;Lehmann et al, 2011). Despite nearly a decade after the introduction of tumorogenicity of CSCs in breast cancer (Al-Hajj et al, 2003), only a few clinical trials have been performed to confirm this hypothesis.…”

Section: 2789 Application Of Stem Cells In Targeted Therapy Of Breasmentioning

confidence: 99%

“…CSCs have been identified and characterized in myeloid leukemia and solid tumors including breast, brain, lung, colon, pancreatic, head and neck cancers (Heppner, 1984;Reya et al, 2001;Al-Hajj et al, 2003;Singh et al, 2003;Dwyer et al, 2007;Li et al, 2007;O'Brien et al, 2007;Prince et al, 2007;Aboody et al, 2008;Nakshatri, 2010), employing typical profile of various surface markers such as CD44, CD133 (Aboody et al, 2008) or ALDH (Balicki, 2007). Breast cancer was the first solid cancer from which CSCs were identified and isolated in combination with flowcytometry by Al-Hajj et al (AlHajj et al, 2003;Lindeman and Visvader, 2010).…”

Section: Introductionmentioning

confidence: 99%