T cell targeting in cancer therapy

Bolhuis, R. L. H.; Sturm, Els; Braakman, Eric

doi:10.1007/bf01741317

Cited by 29 publications

(10 citation statements)

References 109 publications

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“…The therapeutic potential of exogenously administered BsAbs can be limited by their short half-life and poor accessibility to tumor sites (12,13). Moreover, systemic administration of BsAbs can also lead to serious sideeffects and toxicity (14,15) due to the acute release of cytokines.…”

Section: Ellular Immunotherapy Of Malignant Diseases Intends Tomentioning

confidence: 99%

Induction of Human T Lymphocyte Cytotoxicity and Inhibition of Tumor Growth by Tumor-Specific Diabody-Based Molecules Secreted from Gene-Modified Bystander Cells

Blanco

Holliger

Vile

et al. 2003

The Journal of Immunology

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Infiltrating T cells are found in many malignancies, but they appear to be mostly anergic and do not attack the tumor, presumably because of the absence of activation and/or costimulatory signals. We describe a strategy for cellular antitumor immunotherapy by the in situ production of soluble bifunctional Ab-based molecules that activate and retarget T cells to the tumor. We genetically modified cells to simultaneously secrete two bifunctional molecules, a bispecific diabody directed against the carcinoembryonic Ag (CEA) and the CD3ε chain of the TCR (αCEA × αCD3), and a fusion protein comprising the extracellular portion of B7-1 fused to a bivalent anti-CEA diabody (B7-αCEA). Together, αCEA × αCD3 and B7-αCEA proved potent at inducing the activation, proliferation, and survival of primary human T cells. When producer cells were cocultured with primary T cells and CEA+ cancer cells, αCEA × αCD3 and B7-αCEA acted in combination to activate and retarget T cell cytotoxicity and completely abrogate tumor growth in the coculture. Furthermore, the introduction of just a few such producer cells at the tumor site efficiently inhibited the growth of established human colon carcinoma xenografts. Despite a cumbersome generation process, the use of autologous gene-modified producer cells opens the way for a new diabody-based gene therapy strategy of cancer.

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Section: Ellular Immunotherapy Of Malignant Diseases Intends Tomentioning

confidence: 99%

Induction of Human T Lymphocyte Cytotoxicity and Inhibition of Tumor Growth by Tumor-Specific Diabody-Based Molecules Secreted from Gene-Modified Bystander Cells

Blanco

Holliger

Vile

et al. 2003

The Journal of Immunology

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“…[13][14][15] Bispecific antibodies with specificity for the CD3 molecule on T cells and tumor cell surface antigens can also redirect activated T cells to lyse tumor cells. 16 Application of these approaches relies on the identification of tumor-associated antigens that are preferentially expressed on the surface of tumor cells. Intravenous administration of bispecific antibodies can also induce systemic cytokine release and toxicity.…”

Section: Introductionmentioning

confidence: 99%

Activation of lymphocytes by anti-CD3 single-chain antibody dimers expressed on the plasma membrane of tumor cells

Liao

Roffler

2000

Gene Ther

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Activation of cytotoxic T cells without MHC restriction was attempted by expressing single-chain antibodies (scFv) against CD3 on the surface of tumor cells. A chimeric protein consisting of a scFv of mAb 145.2C11, the hinge-CH 2 -CH 3 region of human IgG 1 , and the transmembrane and cytosolic domains of murine CD80 formed disulfide-linked dimers on the plasma membrane of cells and specifically bound lymphocytes. Anti-CD3 scFv dimers expressed on the cell surface induced CD25 (IL-2 receptor ␣-chain) expression and proliferation of splenocytes. CT26 tumor cells engineered to express surface scFv dimers (CT26/2C11) also induced potent lymphocyte cytotoxicity with or without addition of exogenous IL-2. Splenocytes activated by CT26/2C11 cells

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“…Bispecific antibody technology allows the creation of a single antibody directed against both a TA and against a given surface marker on an effector cell, such as CD3 on T cells, or CD16 on NK cells [37]. In theory, these antibodies should help to localize the LAK cells on the tumor via their anti-TA activity.…”

Section: Bispecific Antibody Technologymentioning

confidence: 99%

Strategies to Endow Cytotoxic T Lymphocytes or Natural Killer Cells with Antibody Activity against Carcinoembryonic Antigen

Kuroki¹,

Shibaguchi²,

Badran³

et al. 2004

Tumor Biol

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Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are main effecter cells in cellular immunity against tumor cells. T-cell immunotherapy is based on the assumption that tumor(-associated) antigen (TA) peptides are correctly presented by HLA class I molecules on target tumor cells, and NK cell immunotherapy is based on the hypothesis that cell surface TAs or ligands for NK receptors are widely expressed in tumor cells. However, human tumor cells often lose HLA class I molecules, and target cell ligands for NK receptors are not always expressed in human tumor cells. These altered HLA class I phenotypes and non-ubiquitous expression of NK receptor ligands constitute the major tumor escape mechanism facing tumor-specific CTL and/or NK cell mediated responses. These facts also indicate that it is not easy to eliminate the target tumors only by activating tumor-specific CTLs or NK cells with cancer vaccine treatments. On the other hand, it is easily confirmed by immunohistochemistry whether or not antibody-recognized TAs exist on the cell surface of target tumor cells. Therefore, endowing CTLs or NK cells with antigen-binding specificity of anti-TA antibody is a promising approach for re-targeting the activities of these effector cells to tumor cells in an HLA-independent manner. This review summarizes the following four new strategies for re-targeting CTLs or NK cells to carcinoembryonic-antigen-expressing tumor cells: (1) bispecific antibody technology; (2) antibody-cytokine fusion protein technology; (3) chimeric immune receptor technology, and (4) antibody-HLA/peptide complex technology.

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T cell targeting in cancer therapy

Cited by 29 publications

References 109 publications

Induction of Human T Lymphocyte Cytotoxicity and Inhibition of Tumor Growth by Tumor-Specific Diabody-Based Molecules Secreted from Gene-Modified Bystander Cells

Induction of Human T Lymphocyte Cytotoxicity and Inhibition of Tumor Growth by Tumor-Specific Diabody-Based Molecules Secreted from Gene-Modified Bystander Cells

Activation of lymphocytes by anti-CD3 single-chain antibody dimers expressed on the plasma membrane of tumor cells

Strategies to Endow Cytotoxic T Lymphocytes or Natural Killer Cells with Antibody Activity against Carcinoembryonic Antigen

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