Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells

Cole, Catherine; Qiao, Jian; Kottke, Timothy; Díaz, Rosa María; Ahmed, Atique U.; Sánchez-Pérez, Luis; Brunn, Gregory J.; Thompson, Jill; Chester, John D.; Vile, Richard G.

doi:10.1038/nm1297

Cited by 137 publications

(160 citation statements)

References 44 publications

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“…Such nonspecific binding is of considerable magnitude in vitro and likely contributes to dilution effects and limited target cell transduction efficiency after in vivo particle delivery (31). Indeed, in our own studies we recovered only ϳ10% infectious particles in the non-cell-associated fraction after a 1-h exposure of vector to primary hematopoietic cells, consistent with results by Cole and colleagues (10). Moreover, retention of particles on the cell surface can result in localized secondary transduction in recipients after direct injection of lentivectorexposed cardiomyocytes into brain and muscle tissue (5).…”

Section: Discussionsupporting

confidence: 90%

Prolonged Adherence of Human Immunodeficiency Virus-Derived Vector Particles to Hematopoietic Target Cells Leads to Secondary Transduction In Vitro and In Vivo

Pan¹,

Scarlett²,

Luoh³

et al. 2007

J Virol

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Human immunodeficiency virus type 1-derived lentivirus vectors bearing the vesicular stomatitis virus G (VSV-G) envelope glycoprotein demonstrate a wide host range and can stably transduce quiescent hematopoietic stem cells. In light of concerns about biosafety and potential germ line transmission, they have been used predominantly for ex vivo strategies, thought to ensure the removal of excess surface-bound particles and prevent in vivo dissemination. Studies presented here instead reveal prolonged particle adherence after ex vivo exposure, despite serial wash procedures, with subsequent transduction of secondary target cells in direct and transwell cocultures. We explored the critical parameters affecting particle retention and transfer and show that attachment to the cell surface selectively protects virus particles from serum complement-mediated inactivation. Moreover, studies with nonmyeloablated murine recipients show that transplantation of vectorexposed, washed hematopoietic cells results in systemic dissemination of functional VSV-G/lentivector particles. We demonstrate genetic marking by inadvertent transfer of vector particles and prolonged expression of transgene product in recipient tissues. Our findings have implications for biosafety, vector design, and cell biology research.

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Section: Discussionsupporting

confidence: 90%

Prolonged Adherence of Human Immunodeficiency Virus-Derived Vector Particles to Hematopoietic Target Cells Leads to Secondary Transduction In Vitro and In Vivo

Pan¹,

Scarlett²,

Luoh³

et al. 2007

J Virol

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show abstract

“…These encompass herpes simplex virus-1 in human teratocarcinoma cells, 27 retrovirus in outgrowth endothelial cells, 28 retrovirus on antigen-specifc T cells 29 and modified vaccinia virus in cytokine-induced killer cells. 30 Their relative merit for glioma therapy has yet to be defined.…”

Section: Discussionmentioning

confidence: 99%

Targeted release of oncolytic measles virus by blood outgrowth endothelial cells in situ inhibits orthotopic gliomas

et al. 2007

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Malignant gliomas remain largely incurable despite intensive efforts to develop novel therapies. Replicating oncolytic viruses have shown great promise, among them attenuated measles viruses of the Edmonston B strain (MV-Edm). However, host immune response and the infiltrative nature of gliomas limit their efficacy. We show that human blood outgrowth endothelial cells (BOECs), readily expandable from peripheral blood, are easily infected by MV-Edm and allow replication of MV-Edm while surviving long enough after infection to serve as vehicles for MV-Edm (BOEC/MV-Edm). After intravenous and peritumoral injection, BOEC/MV-Edm deliver the viruses selectively to irradiated orthotopic U87 gliomas in mice. At the tumor, MV-Edm produced by the BOECs infect glioma cells. Subsequent spread from tumor cell to tumor cell leads to focal infection and cytopathic effects that decrease tumor size and, in the case of peritumoral injection, prolong survival of mice. Since MV-Edm within BOECs are not readily neutralized and because BOEC/MVEdm search and destroy glioma cells, BOEC/MV-Edm constitute a promising novel approach for glioma therapy.

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“…In some examples of this approach, the cell itself has therapeutic potential resulting in additive antitumor effects between the carrier and the passenger. 11 Finally, in the most complex scenario, a tumor-targeting, cell-based therapeutic will be used as a carrier vehicle in conjunction with a therapeutic passenger. The combination may have additive effects or the biology of the targeting system and the payload can be integrated leading to synergistic tumor-killing.…”

mentioning

confidence: 99%

Integrating the biological characteristics of oncolytic viruses and immune cells can optimize therapeutic benefits of cell-based delivery

Thorne

Contag

2008

Gene Ther

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Despite significant advances in the development of tumorselective agents, strategies for effective delivery of these agents across biological barriers to cells within the tumor microenvironment has been limiting. One tactical approach to overcoming biological barriers is to use cells as delivery vehicles, and a variety of different cell types have been investigated with a range of agents. In addition to transporting agents with targeted delivery, cells can also produce their own tumoricidal effect, conceal a payload from an immune response, amplify a selective agent at the target site and facilitate an antitumor immune response. We have reported a therapeutic combination consisting of cytokine induced killer cells and an oncolytic vaccinia virus with many of these features that led to therapeutic synergy in animal models of human cancer. The synergy was due to the interaction of the two agents to enhance the antitumor benefits of each individual component. As both of these agents display broad tumor-targeting potential and possess unique tumor killing mechanisms, together they were able to recognize and destroy a far greater number of malignant cells within the heterogeneous tumor than either agent alone. Effective cancer therapy will require recognition and elimination of the root of the disease, the cancer stem cell, and the combination of CIK cells and oncolytic vaccinia viruses has this potential. To create effective tumor-selective agents the viruses are modified to take advantage of the unique biology of the cancer cell. Similarly, if we are to develop targeted therapies that are sufficiently multifaceted to eliminate cancer cells at all stages of disease, we should integrate the virus into the unique biology of the cell delivery vehicle.

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Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells

Cited by 137 publications

References 44 publications

Prolonged Adherence of Human Immunodeficiency Virus-Derived Vector Particles to Hematopoietic Target Cells Leads to Secondary Transduction In Vitro and In Vivo

Prolonged Adherence of Human Immunodeficiency Virus-Derived Vector Particles to Hematopoietic Target Cells Leads to Secondary Transduction In Vitro and In Vivo

Targeted release of oncolytic measles virus by blood outgrowth endothelial cells in situ inhibits orthotopic gliomas

Integrating the biological characteristics of oncolytic viruses and immune cells can optimize therapeutic benefits of cell-based delivery

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