T cell activation by recombinant FcεRI γ-chain immune receptors: an extracellular spacer domain impairs antigen-dependent T cell activation but not antigen recognition

Hombach, Andreas; Heuser, Claudia; Gerken, Martin; Fischer, Boris; Lewalter, K; Diehl, Volker; Pohl, Christoph; Abken, Hinrich

doi:10.1038/sj.gt.3301195

Cited by 49 publications

(36 citation statements)

References 13 publications

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“…Because soluble antigen could interfere with the cIgTCRmediated lysis, 2,40 we examined the cytotoxicity of scBW431/26-hFc -expressing YT cells in the presence of soluble CEA protein. We did not find any inhibition of the tumor cell lysis by soluble CEA protein in concentrations up to 10 g /mL.…”

Section: Cancer Gene Therapymentioning

confidence: 99%

Human natural killer cell line modified with a chimeric immunoglobulin T-cell receptor gene leads to tumor growth inhibition in vivo

Schirrmann

Pecher

2002

Cancer Gene Ther

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The gene transfer of tumor -specific chimeric immunoglobulin T -cell receptors ( cIgTCRs ) combining antibody -like specificity with the effector cell function could be an attractive tool in immunotherapy. In this study, we directed the human natural killer ( NK ) cell line YT to tumor cells by gene transfer of a cIgTCR with specificity against the human carcinoembryonic antigen ( CEA ). The cIgTCR was constructed of a CEA -specific humanized single -chain Fv antibody fragment fused to the IgG1 Fc domain and the CD3 chain. YT cells were transfected with the cIgTCR gene by electroporation and cIgTCR -expressing cells were enriched by immunoaffinity purification. cIgTCR -expressing YT cells specifically lysed CEA + colon carcinoma cell lines, which were resistant to the parental YT cell line. The lysis was not inhibited in the presence of soluble CEA. Receptor gene -modified YT cells retained their CEA -specific cytolytic activity after -irradiation in vitro and inhibited the tumor growth in vivo after adoptive transfer into NOD / SCID mice. This gene -modified NK cell line available in unlimited source might be useful in clinical immunotherapy of CEA + cancer.

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Section: Cancer Gene Therapymentioning

confidence: 99%

Human natural killer cell line modified with a chimeric immunoglobulin T-cell receptor gene leads to tumor growth inhibition in vivo

Schirrmann

Pecher

2002

Cancer Gene Ther

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“…11,14 For retroviral transduction of peripheral blood T cells, the receptor expression cassette (HRS3-scFv-␥; BW431/26-scFv-Fc-␥) was inserted into the retroviral vector pSTITCH. 15,16 To generate GALVpseudotyped retrovirus, 293T cells were cotransfected with the recombinant pSTITCH vector DNA (6 g) and with DNA of the retroviral helper plasmids pHIT and pCOLT (each 6 g DNA/ml), encoding the MMLV gag and pol genes and the GALV envelope gene, respectively. 13 This procedure results in transient production of high titers of infectious retrovirus.…”

Section: Primary Cells Of the Cutaneous T Cell Lymphoma Biopsy Were Cmentioning

confidence: 99%

“…On the other hand, we recently demonstrated that anti-CD30-␥ receptor grafted T cells can be substantially enriched after retroviral transduction utilizing an antiidiotypic mAb with specificity for the receptor's antigen binding domain. 15 Enriched receptor-grafted T cells can be further expanded by short-term culture thereby significantly increasing the number of effector cells for clinical application. Based on the data presented in this report we conclude that anti-CD30-␥ receptor-grafted peripheral blood T cells can be recruited to direct a highly effective and specific antitumor response against autologous CD30 + lymphoma cells.…”

Section: Primary Cells Of the Cutaneous T Cell Lymphoma Biopsy Were Cmentioning

confidence: 99%

T cells engrafted with a recombinant anti-CD30 receptor target autologous CD30+ cutaneous lymphoma cells

et al. 2001

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T cells can be directed to antigen-specific, MHC-independent target cell lysis by grafting with a recombinant receptor with antibody-like specificity. Here, we asked whether T cells from the peripheral blood of a patient with cutaneous T cell lymphoma can be recruited for an immune response against autologous tumor cells. Lymphoma cells with a CD3 − CD4 + CD30 + phenotype and clonal TCR-V␤7 rearrangement were isolated from a cutaneous lesion. The lymphoma lesion additionally harbored CD3 + CD25 + activated normal T cells despite ongoing tumor progression. Keywords: cutaneous T cell lymphoma; adoptive immunotherapy; chimeric receptor, CD30T cells can be equipped with pre-defined binding specificity by grafting with a recombinant receptor that harbors an antibody-derived binding domain and an intracellular signalling domain for cellular activation. The chimeric receptor strategy combines the universal properties of antibodies for specific antigen recognition with highly efficient cellular activation upon antigen-specific receptor crosslinking. To test this strategy for use in the cellular immunotherapy of malignant diseases, a number of in vitro and in vivo systems have been applied. Most of these systems have in common that cells of established tumor cell lines were utilized as a model system (Refs 1-3, for review see Ref. 4). On the other hand, it was recently demonstrated that primary, in situ growing tumors and transplanted tumor cell lines differ substantially in their ability to induce a cellular antitumor response and that tumor cell lines may poorly reflect the clinical situation. 5 Particularily, in situ growing autologous tumor cells are partially or completely tolerized by the immune system and an efficient antitumor response is frequently suppressed during tumor progression. Accordingly, in the case of melanoma substantial populations of tumor-specific CD8 + cytotoxic T cells (CTLs) could be detected despite tumor progression. Tumorspecific CTLs, however, were demonstrated to be functionally anergized 6 and, moreover, melanoma-specific

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“…The PCR products were ligated into the BamHI and XhoI sites of the expression vector pRSV-HRS3-scFv-g, 16 thereby replacing the FceRIg DNA. The HRS3-scFv-Fc DNA was PCR amplified and flanked with SnaBI and BglII restriction sites (underlined) utilizing the pRSV-HRS3-scFv-Fc DNA as template and the oligonucleotides Lkappa-5…”

Section: Cell Linesmentioning

confidence: 99%

Simultaneous targeting of IL2 and IL12 to Hodgkin's lymphoma cells enhances activation of resting NK cells and tumor cell lysis

Hombach

Heuser

Abken

2005

Intl Journal of Cancer

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Hodgkin's disease (HD) is characterized by the accumulation of functionally anergic T cells in the vicinity of the malignant Hodgkin/ Reed-Sternberg (H/RS) cells. To revert cellular anergy against H/RS cells, we generated an anti-CD30-antibody-interleukin-(IL)-2 and an anti-CD30-antibody-IL12 fusion protein that target IL2 and IL12, respectively, specifically to CD30 + H/RS cells. Both antibody-cytokine fusion proteins act cooperatively in the activation of resting NK cells, the induction of IFN-g secretion and enhanced target cell lysis. The cooperative activity of the targeted cytokines suggests that the application of both antibody-cytokine fusion proteins may be particularly suitable for the specific immunotherapy of Hodgkin's lymphoma. ' 2005 Wiley-Liss, Inc.

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T cell activation by recombinant FcεRI γ-chain immune receptors: an extracellular spacer domain impairs antigen-dependent T cell activation but not antigen recognition

Cited by 49 publications

References 13 publications

Human natural killer cell line modified with a chimeric immunoglobulin T-cell receptor gene leads to tumor growth inhibition in vivo

Human natural killer cell line modified with a chimeric immunoglobulin T-cell receptor gene leads to tumor growth inhibition in vivo

T cells engrafted with a recombinant anti-CD30 receptor target autologous CD30+ cutaneous lymphoma cells

Simultaneous targeting of IL2 and IL12 to Hodgkin's lymphoma cells enhances activation of resting NK cells and tumor cell lysis

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