Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes

Verena Labenski; Julia D Suerth; Elke Barczak; Dirk Heckl; Camille Levy; Ornellie Bernadin; Emmanuelle Charpentier; David A Williams; Boris Fehse; Els Verhoeyen; Axel Schambach

doi:10.1016/j.biomaterials.2016.04.019

Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes

Standard

Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes. / Labenski, Verena; Suerth, Julia D; Barczak, Elke; Heckl, Dirk; Levy, Camille; Bernadin, Ornellie; Charpentier, Emmanuelle; Williams, David A; Fehse, Boris; Verhoeyen, Els; Schambach, Axel.

in: BIOMATERIALS, Jahrgang 97, 26.04.2016, S. 97-109.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Labenski, V, Suerth, JD, Barczak, E, Heckl, D, Levy, C, Bernadin, O, Charpentier, E, Williams, DA, Fehse, B, Verhoeyen, E & Schambach, A 2016, 'Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes', BIOMATERIALS, Jg. 97, S. 97-109. https://doi.org/10.1016/j.biomaterials.2016.04.019

APA

Labenski, V., Suerth, J. D., Barczak, E., Heckl, D., Levy, C., Bernadin, O., Charpentier, E., Williams, D. A., Fehse, B., Verhoeyen, E., & Schambach, A. (2016). Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes. BIOMATERIALS, 97, 97-109. https://doi.org/10.1016/j.biomaterials.2016.04.019

Vancouver

Labenski V, Suerth JD, Barczak E, Heckl D, Levy C, Bernadin O et al. Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes. BIOMATERIALS. 2016 Apr 26;97:97-109. https://doi.org/10.1016/j.biomaterials.2016.04.019

Bibtex

@article{2d9c5987714f4c2d8f87c55f2a5ee402,

title = "Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes",

abstract = "Primary human T lymphocytes represent an important cell population for adoptive immunotherapies, including chimeric-antigen and T-cell receptor applications, as they have the capability to eliminate non-self, virus-infected and tumor cells. Given the increasing numbers of clinical immunotherapy applications, the development of an optimal vector platform for genetic T lymphocyte engineering, which allows cost-effective high-quality vector productions, remains a critical goal. Alpharetroviral self-inactivating vectors (ARV) have several advantages compared to other vector platforms, including a more random genomic integration pattern and reduced likelihood for inducing aberrant splicing of integrated proviruses. We developed an ARV platform for the transduction of primary human T lymphocytes. We demonstrated functional transgene transfer using the clinically relevant herpes-simplex-virus thymidine kinase variant TK.007. Proof-of-concept of alpharetroviral-mediated T-lymphocyte engineering was shown in vitro and in a humanized transplantation model in vivo. Furthermore, we established a stable, human alpharetroviral packaging cell line in which we deleted the entry receptor (SLC1A5) for RD114/TR-pseudotyped ARVs to prevent superinfection and enhance genomic integrity of the packaging cell line and viral particles. We showed that superinfection can be entirely prevented, while maintaining high recombinant virus titers. Taken together, this resulted in an improved production platform representing an economic strategy for translating the promising features of ARVs for therapeutic T-lymphocyte engineering.",

author = "Verena Labenski and Suerth, {Julia D} and Elke Barczak and Dirk Heckl and Camille Levy and Ornellie Bernadin and Emmanuelle Charpentier and Williams, {David A} and Boris Fehse and Els Verhoeyen and Axel Schambach",

year = "2016",

month = apr,

day = "26",

doi = "10.1016/j.biomaterials.2016.04.019",

language = "English",

volume = "97",

pages = "97--109",

journal = "BIOMATERIALS",

issn = "0142-9612",

publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes

AU - Labenski, Verena

AU - Suerth, Julia D

AU - Barczak, Elke

AU - Heckl, Dirk

AU - Levy, Camille

AU - Bernadin, Ornellie

AU - Charpentier, Emmanuelle

AU - Williams, David A

AU - Fehse, Boris

AU - Verhoeyen, Els

AU - Schambach, Axel

PY - 2016/4/26

Y1 - 2016/4/26

N2 - Primary human T lymphocytes represent an important cell population for adoptive immunotherapies, including chimeric-antigen and T-cell receptor applications, as they have the capability to eliminate non-self, virus-infected and tumor cells. Given the increasing numbers of clinical immunotherapy applications, the development of an optimal vector platform for genetic T lymphocyte engineering, which allows cost-effective high-quality vector productions, remains a critical goal. Alpharetroviral self-inactivating vectors (ARV) have several advantages compared to other vector platforms, including a more random genomic integration pattern and reduced likelihood for inducing aberrant splicing of integrated proviruses. We developed an ARV platform for the transduction of primary human T lymphocytes. We demonstrated functional transgene transfer using the clinically relevant herpes-simplex-virus thymidine kinase variant TK.007. Proof-of-concept of alpharetroviral-mediated T-lymphocyte engineering was shown in vitro and in a humanized transplantation model in vivo. Furthermore, we established a stable, human alpharetroviral packaging cell line in which we deleted the entry receptor (SLC1A5) for RD114/TR-pseudotyped ARVs to prevent superinfection and enhance genomic integrity of the packaging cell line and viral particles. We showed that superinfection can be entirely prevented, while maintaining high recombinant virus titers. Taken together, this resulted in an improved production platform representing an economic strategy for translating the promising features of ARVs for therapeutic T-lymphocyte engineering.

AB - Primary human T lymphocytes represent an important cell population for adoptive immunotherapies, including chimeric-antigen and T-cell receptor applications, as they have the capability to eliminate non-self, virus-infected and tumor cells. Given the increasing numbers of clinical immunotherapy applications, the development of an optimal vector platform for genetic T lymphocyte engineering, which allows cost-effective high-quality vector productions, remains a critical goal. Alpharetroviral self-inactivating vectors (ARV) have several advantages compared to other vector platforms, including a more random genomic integration pattern and reduced likelihood for inducing aberrant splicing of integrated proviruses. We developed an ARV platform for the transduction of primary human T lymphocytes. We demonstrated functional transgene transfer using the clinically relevant herpes-simplex-virus thymidine kinase variant TK.007. Proof-of-concept of alpharetroviral-mediated T-lymphocyte engineering was shown in vitro and in a humanized transplantation model in vivo. Furthermore, we established a stable, human alpharetroviral packaging cell line in which we deleted the entry receptor (SLC1A5) for RD114/TR-pseudotyped ARVs to prevent superinfection and enhance genomic integrity of the packaging cell line and viral particles. We showed that superinfection can be entirely prevented, while maintaining high recombinant virus titers. Taken together, this resulted in an improved production platform representing an economic strategy for translating the promising features of ARVs for therapeutic T-lymphocyte engineering.

U2 - 10.1016/j.biomaterials.2016.04.019

DO - 10.1016/j.biomaterials.2016.04.019

M3 - SCORING: Journal article

C2 - 27162078

VL - 97

SP - 97

EP - 109

JO - BIOMATERIALS

JF - BIOMATERIALS

SN - 0142-9612

ER -