A retroviral vector system ‘STITCH’ in combination with an optimized single chain antibody chimeric receptor gene structure allows efficient gene transduction and expression in human T lymphocytes

Weijtens, M. E. M.; Willemsen, Ralph A.; Hart, E.; Bolhuis, R. L. H.

doi:10.1038/sj.gt.3300696

Cited by 95 publications

(107 citation statements)

References 20 publications

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“…15 The colon carcinoma cell lines LS174T (ATCC CCL 188), SW948 (ATCC CCL 237) and H716 (ATCC CCL-251) and the human acute monocytic leukaemia cell line THP-1 (ATCC TIB-202) were obtained from ATCC, Rockville, MD, USA. The CD30 + lymphoma line MyLa was kindly provided by Professor R Dummer, Zurich.…”

Section: Cell Lines and Reagentsmentioning

confidence: 99%

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Adoptive immunotherapy with genetically engineered T cells: modification of the IgG1 Fc ‘spacer’ domain in the extracellular moiety of chimeric antigen receptors avoids ‘off-target’ activation and unintended initiation of an innate immune response

2010

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Section: Cell Lines and Reagentsmentioning

confidence: 99%

“…Retroviral transduction of T cells with recombinant receptors was elsewhere described in detail. 15,[19][20][21][22] Receptor expression was monitored by flow cytometry.…”

Section: Generation Of Carsmentioning

confidence: 99%

Adoptive immunotherapy with genetically engineered T cells: modification of the IgG1 Fc ‘spacer’ domain in the extracellular moiety of chimeric antigen receptors avoids ‘off-target’ activation and unintended initiation of an innate immune response

2010

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“…[16][17][18] Such ch-Rec consists of a mAb-based single chain antibody (scFv), coupled to a Fc(⑀)RI ␥-chain or CD3 -chain, and these ch-Rec can functionally be expressed in the membrane of primary human T lymphocytes. [19][20][21][22][23] As for endogenous TCRs, binding of ch-Rec to relevant TAA results in activation of lymphocyte functions, eg target cell lysis and lymphokine production. [19][20][21][22][23][24] The ch-Rec-mediated antigen binding is MHC-unrestricted and of high affinity.…”

Section: Introductionmentioning

confidence: 99%

“…[19][20][21][22][23] As for endogenous TCRs, binding of ch-Rec to relevant TAA results in activation of lymphocyte functions, eg target cell lysis and lymphokine production. [19][20][21][22][23][24] The ch-Rec-mediated antigen binding is MHC-unrestricted and of high affinity. Moreover, adoptive transfer of genetically engineered ch-Rec POS CTLs has shown in vivo antitumor activity in mice.…”

Section: Introductionmentioning

confidence: 99%

“…[21][22][23] In order to optimize the generation of primary human CTLs with genetically engineered tumor specificity and anti-tumor activity, we developed a retroviral vector system that produces high gene expression and high membrane expression of the ch-Rec by primary human T lymphocytes. 23 Because tumor cells in vivo express TAA at varying densities we determined how different densities of TAA tumor cells on the one hand and ch-Rec and T lymphocytes on the other affect the quantity and quality of T lymphocyte responses, which are important in anti-cancer immune activities.…”

Section: Introductionmentioning

confidence: 99%

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Functional balance between T cell chimeric receptor density and tumor associated antigen density: CTL mediated cytolysis and lymphokine production

2000

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Genetically engineered expression of tumor-specific single chain antibody chimeric receptors (ch-Rec) on human T lymphocytes endow these cells with the parental monoclonal antibody (mAb) dictated tumor specificity and may be useful for clinical immuno-genetherapy. Therefore it was of importance to assess how the densities of tumor-specific receptors and tumor associated antigens (TAA), respectively, affect primary human T lymphocyte functions in relation to target cell susceptibilities to lysis. We therefore studied the functional balance between ch-Rec densities on human T lymphocytes and TAA on tumor cells. The gene construct encoding a ch-Rec derived from (1) a renal carcinoma cell (RCC) specific mouse mAb (G250), and (2) the human signal transducing Fc(⑀)RI ␥-chain was used. To obtain chRec HIGH-POS and ch-Rec LOW-POS T lymphocytes, two distinct retroviral vectors were used to introduce the gene constructs into primary human T lymphocytes. Levels of ch-Rec-

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An entirely humanized CD3 ζ-chain signaling receptor that directs peripheral blood t cells to specific lysis of carcinoembryonic antigen-positive tumor cells

et al. 2000

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Recombinant T‐cell receptors with antibody‐like specificity for tumor‐associated antigens are successfully used to direct the cytolytic activity of T cells toward tumor cells. Clinical application, however, needs to comply with the low immunogenicity of the recombinant receptor, efficient gene transfer into peripheral blood T cells, and enrichment of receptor‐grafted cells. Here, we address these issues and describe an entirely humanized immune receptor for use in adoptive immunotherapy of colorectal carcinoma. The receptor consists of a single‐chain antibody (scFv) binding domain specific for carcinoembryonic antigen (CEA), the IgG hinge and CH2/CH3 (Fc) joining region, and the transmembrane and intracellular CD3 ζ signaling chain. To express the receptor in peripheral blood T cells, both GALV envelope and MuLV 4070A pseudotyped retrovirus turned out to be equally efficient, with transduction efficiencies of about 5% to 40%, depending on the lymphocyte donor. Furthermore, receptor‐grafted T cells could be 2‐ to 6‐fold enriched by magnetic activated cell sorting, utilizing an antibody directed to the extracellular IgG domain of the receptor. Upon co‐culture with CEA+ tumor cells, receptor‐grafted T cells are specifically and efficiently activated to cytolysis and IFN‐γ secretion, demonstrating their feasibility for the adoptive immunotherapy of CEA+ carcinomas. Int. J. Cancer 88:115–120, 2000. © 2000 Wiley‐Liss, Inc.

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A retroviral vector system ‘STITCH’ in combination with an optimized single chain antibody chimeric receptor gene structure allows efficient gene transduction and expression in human T lymphocytes

Cited by 95 publications

References 20 publications

Adoptive immunotherapy with genetically engineered T cells: modification of the IgG1 Fc ‘spacer’ domain in the extracellular moiety of chimeric antigen receptors avoids ‘off-target’ activation and unintended initiation of an innate immune response

Adoptive immunotherapy with genetically engineered T cells: modification of the IgG1 Fc ‘spacer’ domain in the extracellular moiety of chimeric antigen receptors avoids ‘off-target’ activation and unintended initiation of an innate immune response

Functional balance between T cell chimeric receptor density and tumor associated antigen density: CTL mediated cytolysis and lymphokine production

An entirely humanized CD3 ζ-chain signaling receptor that directs peripheral blood t cells to specific lysis of carcinoembryonic antigen-positive tumor cells

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