Human melanoma therapy in the SCID mouse:In vivo targeting and reactivation of melanoma-specific cytotoxic T cells by bi-specific antibody fragments

Cochlovius, Björn; Perschl, Astrid; Adema, Gosse J.; Zöller, Margot

doi:10.1002/(sici)1097-0215(19990505)81:3<486::aid-ijc25>3.0.co;2-p

Cited by 14 publications

(5 citation statements)

References 27 publications

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“…T cell signaling via the TCR alone without a costimulatory signal can lead to anergy (48) or even activation-induced cell death (49). Furthermore, recent experiments demonstrated that costimulation via CD28 together with anti-CD3 ϫ antitumor BsAb prevents apoptosis in the targeted T cells (50) and even reactivates exhausted tumor-reactive CTL in an in vivo model of human melanoma (42). Impressive results were also obtained using anti-CD28 ϫ antitumor BsAb together with anti-CD3 ϫ antitumor BsAb for curing human primary tumors (43) and metastases (42) in immunodeficient mice.…”

Section: Discussionmentioning

confidence: 99%

“…4A). Several authors have shown that T cells, redirected against tumor cells with bispecific antitumor ϫ anti-CD3 Abs, can be effectively costimulated using anti-CD28 mAb or antitumor ϫ anti-CD28 BsAb to increase their cytolytic activity (5,41,42). We therefore investigated whether the addition of anti-CD28 mAb 15E8 in a concentration of 1 g/ml to the effector cell population could increase target cell lysis.…”

Section: Biological Activity Of Cd3 ϫ Cd19 Diabodymentioning

confidence: 99%

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Treatment of Human B Cell Lymphoma Xenografts with a CD3 × CD19 Diabody and T Cells

Cochlovius

Kipriyanov

Stassar

et al. 2000

The Journal of Immunology

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The use of anti-CD3 × antitumor bispecific Abs is an attractive and highly specific approach in cancer therapy. Recombinant Ab technology now provides powerful tools to enhance the potency of such immunotherapeutic constructs. We designed a heterodimeric diabody specific for human CD19 on B cells and CD3ε chain of the TCR complex. After production in Escherichia coli and purification, we analyzed its affinity, stability, and pharmacokinetics, and tested its capacity to stimulate T cell proliferation and mediate in vitro lysis of CD19+ tumor cells. The effect of the diabody on tumor growth was investigated in an in vivo model using immunodeficient mice bearing a human B cell lymphoma. The CD3 × CD19 diabody specifically interacted with both CD3- and CD19-positive cells, was able to stimulate T cell proliferation in the presence of tumor cells, and induced the lysis of CD19+ cells in the presence of activated human PBL. The lytic potential of the diabody was enhanced in the presence of an anti-CD28 mAb. In vivo experiments indicated a higher stability and longer blood retention of diabodies compared with single chain Fv fragments. Treatment of immunodeficient mice bearing B lymphoma xenografts with the diabody and preactivated human PBL efficiently inhibited tumor growth. The survival time was further prolonged by including the anti-CD28 mAb. The CD3 × CD19 diabody is a powerful tool that should facilitate the immunotherapy of minimal residual disease in patients with B cell leukemias and malignant lymphomas.

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Section: Discussionmentioning

confidence: 99%

Section: Biological Activity Of Cd3 ϫ Cd19 Diabodymentioning

confidence: 99%

Treatment of Human B Cell Lymphoma Xenografts with a CD3 × CD19 Diabody and T Cells

Cochlovius

Kipriyanov

Stassar

et al. 2000

The Journal of Immunology

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“…The use of bi-specific antibodies to target human effector cells to the site of the tumor have also been examined using human-SCID chimeric models (137)(138)(139)(140). In this scenario, the monoclonal antibody is engineered to have dual-specificity for a molecule expressed by the tumor (CD19, c-erb-B2, etc.)…”

Section: Bi-specific Antibodiesmentioning

confidence: 99%

SCID mouse models to study human cancer pathogenesis and approaches to therapy: potential, limitations, and future directions

Richard¹

2002

Front Biosci

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The successful engraftment of human tumors and human immunocompetent cells into severe combined immunodeficient (SCID) mice has led to the generation of a wide array of different experimental designs that have proven useful in studying the cell biology of human cancer, and for evaluating novel therapeutic approaches to the treatment of cancer. In this review five of the most frequently used embodiments of the SCID model are presented. The goals of this review are to discuss how each model has been utilized to study human cancer and its response to many different novel therapies, to provide an assessment of the strengths and limitations of each model, and to outline future directions with a focus on what is needed to overcome some of the current limitations and pitfalls of the SCID models.

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“…In terms of therapeutic efficacy, we observed that adoptive transfer of aAPC induced Mart-1 specific CTL decreased the tumor growth significantly both in prevention and treatment experiments. Various groups have reported the importance of IL-2 for survival and function of transferred CTL in vivo in both animal models [48][49][50] and in patients [45]. The infusion of ex vivo expanded tumor specific T cells have been found to mediate tumor regression successfully in patients with metastatic melanoma in different settings [10,11,22,45,47].…”

Section: Discussionmentioning

confidence: 99%

“…While the human/ SCID models are by their nature only partially reconstituted immune responses, they are proven to be useful in evaluating the therapeutic efficacy of adoptively transferred human tumor specific T cells. These models have been used extensively in studying adoptive immunotherapeutic treatment approaches for diseases including but not limited to EBVassociated lymphoma, B cell lymphoma, adenocarcinoma and melanoma [31,48,49,[51][52][53]. Anti-tumor efficacy of adoptively transferred CTL has been demonstrated in other immunocompetent animal models such as pmel-1 CD8 + antigen specific cells in C57BL/6 host [50,54].…”

Section: Discussionmentioning

confidence: 99%

In vivo functional efficacy of tumor-specific T cells expanded using HLA-Ig based artificial antigen presenting cells (aAPC)

Durai¹,

Krueger

et al. 2008

Cancer Immunol Immunother

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Adoptive immunotherapy for treatment of cancers and infectious diseases is often hampered by a high degree of variability in the final T cell product and in the limited in vivo function and survival of ex vivo expanded antigen-specific cytotoxic T cells (CTL). This has stimulated interest in development of standardized artificial antigen presenting cells (aAPC) to reliably expand antigen specific CTL. However, for successful immunotherapy the aAPC ex vivo generated CTL must have anti-tumor activity in vivo. Here, we demonstrate that HLA-Ig based aAPC stimulated tumor-specific CTL from human peripheral blood T lymphocytes showed robust expansion and functional activity in a human/SCID mouse melanoma model. HLA-Ig based aAPC expanded CTL were detected in the peripheral blood up to 15 days after transfer. Non-invasive bioluminescence imaging of tumor bearing mice demonstrated antigen dependent localization of transferred CTL to the tumor site. Moreover, adoptive transfer of HLA-Ig based aAPC generated CTL inhibited the tumor growth both in prevention and treatment modes of therapy and was comparable to that achieved by dendritic cell expanded CTL. Thus, our data demonstrate potential therapeutic in vivo activity of HLA-Ig based aAPC expanded CTL to control tumor growth.

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Human melanoma therapy in the SCID mouse:In vivo targeting and reactivation of melanoma-specific cytotoxic T cells by bi-specific antibody fragments

Cited by 14 publications

References 27 publications

Treatment of Human B Cell Lymphoma Xenografts with a CD3 × CD19 Diabody and T Cells

Treatment of Human B Cell Lymphoma Xenografts with a CD3 × CD19 Diabody and T Cells

SCID mouse models to study human cancer pathogenesis and approaches to therapy: potential, limitations, and future directions

In vivo functional efficacy of tumor-specific T cells expanded using HLA-Ig based artificial antigen presenting cells (aAPC)

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