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1

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T cell activation upon exposure to patient-derived tumor tissue: A functional assay to select patients for adoptive T cell therapy

Schroten, Caroline ; Kraaij, Robert ; Veldhoven, Joke L.M. ; [et al.]

Elsevier BV ; 2010

In: Journal of Immunological Methods Vol. 359, No. 1-2 ( 2010-07), p. 11-20

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In: Journal of Immunological Methods, Elsevier BV, Vol. 359, No. 1-2 ( 2010-07), p. 11-20

Type of Medium: Online Resource

ISSN: 0022-1759

URL: Article

DOI: 10.1016/j.jim.2010.04.006

RVK:

XA 10000

Language: English

Publisher: Elsevier BV

Publication Date: 2010

detail.hit.zdb_id: 1500495-8

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2

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Protocol for gene transduction and expansion of human T lymphocytes for clinical immunogene therapy of cancer

Lamers, Cor H J ; Willemsen, Ralph A ; Luider, Barbara A ; [et al.]

Springer Science and Business Media LLC ; 2002

In: Cancer Gene Therapy Vol. 9, No. 7 ( 2002-07-01), p. 613-623

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In: Cancer Gene Therapy, Springer Science and Business Media LLC, Vol. 9, No. 7 ( 2002-07-01), p. 613-623

Type of Medium: Online Resource

ISSN: 0929-1903 , 1476-5500

URL: Article

DOI: 10.1038/sj.cgt.7700477

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2002

detail.hit.zdb_id: 1212513-1

detail.hit.zdb_id: 2004200-0

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3

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Highly efficient redirected anti-tumor activity of human lymphocytes transduced with a completely human chimeric immune receptor

Turatti, Fabio ; Figini, Mariangela ; Alberti, Paola ; [et al.]

Wiley ; 2005

In: The Journal of Gene Medicine Vol. 7, No. 2 ( 2005-02), p. 158-170

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In: The Journal of Gene Medicine, Wiley, Vol. 7, No. 2 ( 2005-02), p. 158-170

Type of Medium: Online Resource

ISSN: 1099-498X , 1521-2254

URL: Issue

URL: Journal

URL: Article

DOI: 10.1002/jgm.v7:2

DOI: 10.1002/(ISSN)1521-2254

DOI: 10.1002/jgm.647

Language: English

Publisher: Wiley

Publication Date: 2005

detail.hit.zdb_id: 2002203-7

SSG: 12

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4

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Reprogramming T Lymphocytes for Melanoma Adoptive Immunotherapy by T-Cell Receptor Gene Transfer with Lentiviral Vectors

Bobisse, Sara ; Rondina, Maria ; Merlo, Anna ; [et al.]

American Association for Cancer Research (AACR) ; 2009

In: Cancer Research Vol. 69, No. 24 ( 2009-12-15), p. 9385-9394

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In: Cancer Research, American Association for Cancer Research (AACR), Vol. 69, No. 24 ( 2009-12-15), p. 9385-9394

Abstract: T-cell receptor (TCR) gene transfer for cancer immunotherapy is limited by the availability of large numbers of tumor-specific T cells. TCR α and β chains were isolated from a highly lytic HLA-A2–restricted cytotoxic T lymphocyte (CTL) clone recognizing the melanoma-associated Melan-A/MART-1 antigen and inserted into a lentiviral vector carrying a bidirectional promoter capable of robust and coordinated expression of the two transgenes. Lentiviral vector–based gene delivery systems have shown increased transfer efficiency and transgene expression compared with the widely used γ-retroviral vectors. This vector performed more efficiently than a γ-retrovirus–based vector containing the same expression cassette, resulting in a T-cell population with 60% to 80% of transgenic TCR expression with mainly CD8+ intermediate effector phenotype. Transgenic T cells specifically produced cytokine in response to and killed antigen-expressing melanoma cells, retained an overlapping functional avidity in comparison with the TCR donor CTL clone, and exerted significant therapeutic effects in vivo upon adoptive transfer in melanoma-bearing severe combined immunodeficient mice. Optical imaging showed their accumulation in the tumor site. Overall, our results indicate that lentiviral vectors represent a valid tool for stable and high-intensity expression of transgenic TCR and support clinical exploitation of this approach for therapeutic application. [Cancer Res 2009;69(24):9385–94]

Type of Medium: Online Resource

ISSN: 0008-5472 , 1538-7445

URL: Article

DOI: 10.1158/0008-5472.CAN-09-0494

RVK:

XA 36000

RVK:

XA 10000

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2009

detail.hit.zdb_id: 2036785-5

detail.hit.zdb_id: 1432-1

detail.hit.zdb_id: 410466-3

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5

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Gibbon Ape Leukemia Virus Poorly Replicates in Primary Human T Lymphocytes : Implications for Safety Testing of Primary Human T Lymphocytes Transduced With GALV-pseudotyped Vectors

Lamers, Cor H. J. ; Willemsen, Ralph A. ; van Elzakker, Pascal M. M. L. ; [et al.]

Ovid Technologies (Wolters Kluwer Health) ; 2009

In: Journal of Immunotherapy Vol. 32, No. 3 ( 2009-04), p. 272-279

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In: Journal of Immunotherapy, Ovid Technologies (Wolters Kluwer Health), Vol. 32, No. 3 ( 2009-04), p. 272-279

Type of Medium: Online Resource

ISSN: 1524-9557

URL: Article

DOI: 10.1097/CJI.0b013e318199840a

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2009

detail.hit.zdb_id: 2048797-6

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6

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CD8α Coreceptor to Improve TCR Gene Transfer to Treat Melanoma: Down-Regulation of Tumor-Specific Production of IL-4, IL-5, and IL-10

Willemsen, Ralph A. ; Sebestyén, Zsolt ; Ronteltap, Cees ; [et al.]

The American Association of Immunologists ; 2006

In: The Journal of Immunology Vol. 177, No. 2 ( 2006-07-15), p. 991-998

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In: The Journal of Immunology, The American Association of Immunologists, Vol. 177, No. 2 ( 2006-07-15), p. 991-998

Abstract: Therapeutic success of TCR gene transfer to treat tumors depends on the ability of redirected T cells to become activated upon tumor recognition in vivo. Help provided by tumor-specific Th1 cells is reported to relieve T cells from an anergized state and to induce tumor regression. We recently demonstrated the ability to generate melanoma-specific Th1 cells by genetic introduction of both a CD8-dependent TCR and the CD8α coreceptor into CD4+ T cells. In this study, we analyzed a TCR that binds Ag independently of CD8, a property generally preferred to induce tumor-specific T cell responses, and addressed the contribution of CD8α following introduction into TCR-transduced CD4+ T cells. To this end, primary human CD4+ T cells were gene transferred with a high-avidity TCR, and were shown not only to bind peptide/MHC class I, but also to effectively kill Ag-positive tumor cells in the absence of CD8α. The introduction of CD8α up-regulates the tumor-specific production of TNF-α and IL-2 to some extent, but significantly down-regulates production of IL-4, IL-5, and IL-10 in CD4+ T cells. The introduction of a mutated cysteine motif in CD8α, which prevents its binding to LCK and linker for activation of T cells, did not adversely affect expression and T cell cytotoxicity, but counteracted the CD8α-mediated down-regulation of IL-4 and IL-5, but not IL-10. In conclusion, CD8α down-regulates the production of major Th2-type cytokines, in part mediated by LCK and/or linker for activation of T cells, and may induce differentiation of tumor-specific Th1 cells, which makes this coreceptor an interesting candidate to improve the clinical potential of TCR gene transfer to treat cancer.

Type of Medium: Online Resource

ISSN: 0022-1767 , 1550-6606

URL: Article

DOI: 10.4049/jimmunol.177.2.991

RVK:

XA 54100

RVK:

XA 10000

Language: English

Publisher: The American Association of Immunologists

Publication Date: 2006

detail.hit.zdb_id: 1475085-5

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7

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Multi-component Polymeric System for Tumour Cell-Specific Gene Delivery Using a Universal Bungarotoxin Linker

Willemsen, Ralph A. ; Pechar, Michal ; Carlisle, Robert C. ; [et al.]

Springer Science and Business Media LLC ; 2010

In: Pharmaceutical Research Vol. 27, No. 11 ( 2010-11), p. 2274-2282

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In: Pharmaceutical Research, Springer Science and Business Media LLC, Vol. 27, No. 11 ( 2010-11), p. 2274-2282

Type of Medium: Online Resource

ISSN: 0724-8741 , 1573-904X

URL: Article

DOI: 10.1007/s11095-010-0088-8

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2010

detail.hit.zdb_id: 2036232-8

SSG: 15,3

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8

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Molecular Design of the Cαβ Interface Favors Specific Pairing of Introduced TCRαβ in Human T Cells

Voss, Ralf-Holger ; Willemsen, Ralph A. ; Kuball, Jürgen ; [et al.]

The American Association of Immunologists ; 2008

In: The Journal of Immunology Vol. 180, No. 1 ( 2008-01-01), p. 391-401

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In: The Journal of Immunology, The American Association of Immunologists, Vol. 180, No. 1 ( 2008-01-01), p. 391-401

Abstract: A promising approach to adoptive transfer therapy of tumors is to reprogram autologous T lymphocytes by TCR gene transfer of defined Ag specificity. An obstacle, however, is the undesired pairing of introduced TCRα- and TCRβ-chains with the endogenous TCR chains. These events vary depending on the individual endogenous TCR and they not only may reduce the levels of cell surface-introduced TCR but also may generate hybrid TCR with unknown Ag specificities. We show that such hybrid heterodimers can be generated even by the pairing of human and mouse TCRα- and TCRβ-chains. To overcome this hurdle, we have identified a pair of amino acid residues in the crystal structure of a TCR that lie at the interface of associated TCR Cα and Cβ domains and are related to each other by both a complementary steric interaction analogous to a “knob-into-hole” configuration and the electrostatic environment. We mutated the two residues so as to invert the sense of this interaction analogous to a charged “hole-into-knob” configuration. We show that this inversion in the CαCβ interface promotes selective assembly of the introduced TCR while preserving its specificity and avidity for Ag ligand. Noteworthily, this TCR modification was equally efficient on both a Mu and a Hu TCR. Our data suggest that this approach is generally applicable to TCR independently of their Ag specificity and affinity, subset distribution, and species of origin. Thus, this strategy may optimize TCR gene transfer to efficiently and safely reprogram random T cells into tumor-reactive T cells.

Type of Medium: Online Resource

ISSN: 0022-1767 , 1550-6606

URL: Article

DOI: 10.4049/jimmunol.180.1.391

RVK:

XA 54100

RVK:

XA 10000

Language: English

Publisher: The American Association of Immunologists

Publication Date: 2008

detail.hit.zdb_id: 1475085-5

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9

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TCR transfer induces TCR-mediated tonic inhibition of RAG genes in human T cells

Orlando, Luca ; Accomasso, Lisa ; Circosta, Paola ; [et al.]

Elsevier BV ; 2011

In: Molecular Immunology Vol. 48, No. 12-13 ( 2011-07), p. 1369-1376

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In: Molecular Immunology, Elsevier BV, Vol. 48, No. 12-13 ( 2011-07), p. 1369-1376

Type of Medium: Online Resource

ISSN: 0161-5890

URL: Article

DOI: 10.1016/j.molimm.2011.02.015

Language: English

Publisher: Elsevier BV

Publication Date: 2011

detail.hit.zdb_id: 2013448-4

SSG: 12

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10

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T cell receptor gene therapy: strategies for optimizing transgenic TCR pairing

Govers, Coen ; Sebestyén, Zsolt ; Coccoris, Miriam ; [et al.]

Elsevier BV ; 2010

In: Trends in Molecular Medicine Vol. 16, No. 2 ( 2010-2), p. 77-87

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In: Trends in Molecular Medicine, Elsevier BV, Vol. 16, No. 2 ( 2010-2), p. 77-87

Type of Medium: Online Resource

ISSN: 1471-4914

URL: Article

DOI: 10.1016/j.molmed.2009.12.004

Language: English

Publisher: Elsevier BV

Publication Date: 2010

detail.hit.zdb_id: 2155736-6

SSG: 12

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