Human Pluripotent Stem Cells Produce Natural Killer Cells That Mediate Anti-HIV-1 Activity by Utilizing Diverse Cellular Mechanisms

Ni, Zhenya; Knorr, David A.; Clouser, Christine L.; Hexum, Melinda K.; Southern, Peter J.; Mansky, Louis M.; Park, In Hyun; Kaufman, Dan S.

doi:10.1128/jvi.01774-10

Cited by 83 publications

(67 citation statements)

References 55 publications

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“…89 NK cell populations from human embryonic stem cells or from induced pluripotent stem cells, may have therapeutic application in control of ongoing HIV-1 infection because in vitro studies have shown suppression of HIV-1 infection by three different mechanisms: direct lysis of HIV-1-infected cells, antibody-dependent cellular cytotoxicity, and through production of chemokines and cytokines. 90 It is also conceivable that induction and expansion of NK populations at exposed FRT mucosal surfaces could contribute directly to resistance to HIV-1 infection by elimination of infected cells before amplification and virus dissemination can occur. …”

Section: Immune Components At Epithelial Surfaces Innate Immunitymentioning

confidence: 99%

Coming of age: reconstruction of heterosexual HIV-1 transmission in human ex vivo organ culture systems

et al. 2011

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Section: Immune Components At Epithelial Surfaces Innate Immunitymentioning

confidence: 99%

Coming of age: reconstruction of heterosexual HIV-1 transmission in human ex vivo organ culture systems

et al. 2011

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“…To study lymphocyte trafficking in a mouse xenograft model, we used a well-characterized differentiation protocol to derive NK cells from hESCs [2,3,5]. We have previously demonstrated the derivation and function of NK from both hESCs and iPSCs [3,5].…”

Section: Generation Of Nk Cells From Luciferase-expressing Hescs For mentioning

confidence: 99%

“…We have previously demonstrated the derivation and function of NK from both hESCs and iPSCs [3,5]. hESC-derived NK cells have a potent antitumor activity both in vitro and in vivo.…”

Section: Generation Of Nk Cells From Luciferase-expressing Hescs For mentioning

confidence: 99%

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Engineered Human Embryonic Stem Cell-Derived Lymphocytes to Study In Vivo Trafficking and Immunotherapy

Knorr

Bock

Brentjens

et al. 2013

Stem Cells and Development

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Human embryonic stem cell (hESC)-derived natural killer (NK) cells are a promising source of antitumor lymphocytes for immunotherapeutics. They also provide a genetically tractable platform well suited for the study of antitumor immunotherapies in preclinical models. We have previously demonstrated the potency of hESC-derived NK cells in vivo. Here we use both bioluminescent and fluorescent imaging to demonstrate trafficking of hESC-derived NK cells to tumors in vivo. Our dual-imaging approach allowed us to more specifically define the kinetics of NK cell trafficking to tumor sites. NK cell persistence and trafficking were further evaluated by flow cytometry and immunohistochemistry. This integrated approach provides a unique system to apply the use of human pluripotent stem cells to study the kinetics and biodistribution of adoptively transferred lymphocytes, advances broadly applicable to the field of immunotherapy.

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“…Killer cell Ig-like receptors (KIRs) and CD94/NKG2 heterodimers are two major receptor types that interact with MHC on target cells. For iPSC, however, the yield is considerably lower than for ESC (Ni et al, 2011). …”

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confidence: 96%

Lymphoid Regeneration from Gene-Corrected SCID-X1 Subject-Derived iPSCs

et al. 2015

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Summary X-Linked severe combined immunodeficiency (SCID-X1) is a genetic disease that leaves newborns at high risk of serious infection and a predicted lifespan of less than one year in the absence of a matched bone marrow donor. The disease pathogenesis is due to mutations in the gene encoding the Interleukin-2 receptor gamma chain (IL-2Rγ) leading to a lack of functional lymphocytes. With the leukemogenic concerns of viral gene therapy there is a need to explore alternative therapeutic options. We have utilized induced pluripotent stem cell (iPSC) technology and genome editing mediated by TALENs to generate isogenic patient-specific mutant and gene corrected iPSC lines. While the patient-derived mutant iPSC have the capacity to generate hematopoietic precursors and myeloid cells, only wild-type and gene-corrected iPSC can additionally generate mature NK-cells and T-cell precursors expressing the correctly spliced IL-2Rγ. This study highlights the potential for the development of autologous cell therapy for SCID-X1 patients.

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Human Pluripotent Stem Cells Produce Natural Killer Cells That Mediate Anti-HIV-1 Activity by Utilizing Diverse Cellular Mechanisms

Cited by 83 publications

References 55 publications

Coming of age: reconstruction of heterosexual HIV-1 transmission in human ex vivo organ culture systems

Coming of age: reconstruction of heterosexual HIV-1 transmission in human ex vivo organ culture systems

Engineered Human Embryonic Stem Cell-Derived Lymphocytes to Study In Vivo Trafficking and Immunotherapy

Lymphoid Regeneration from Gene-Corrected SCID-X1 Subject-Derived iPSCs

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