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Your search keyword '"Diabody Anti-CD3"' showing total 2 results
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2 results on '"Diabody Anti-CD3"'

1. Redirection of CD4+ and CD8+ T lymphocytes via an anti-CD3 × anti-CD19 bi-specific antibody combined with cytosine arabinoside and the efficient lysis of patient-derived B-ALL cells.

Author

Dongmei Fan, Wei Li, Yuqi Yang, Xiaolong Zhang, Qing Zhang, Yan Yan, Ming Yang, Jianxiang Wang, and Dongsheng Xiong

Subjects
*LYMPHOBLASTIC leukemia treatment, *CYTARABINE, *CANCER chemotherapy, *IMMUNOTHERAPY, *LYSIS, *CYTOKINES, *CLINICAL trials
Abstract

Background: B-acute lymphoblastic leukemia (B-ALL) is derived from B cell progenitors. Recently, the development of appropriate combinations of chemotherapy and immunotherapy represents a promising approach for eliminating cancer. We previously constructed an anti-CD3 × anti-CD19 bi-specific antibody in a diabody configuration and its disulfide-stabilized format (ds-diabody). The combination of the diabody or ds-diabody and Ara-C was highly effective in enhancing the cytotoxicity of T cells against the CD19+ human leukemia cell-line, Nalm-6, both in vitro and in vivo. This study verified whether B-ALL patient-derived cells were sensitive to the diabody or ds-diabody and low-dosage Ara-C combination. Methods: This study aimed to detect the B7 family members B7.1 (CD80) and B7.2 (CD86) that were expressed in B-ALL patient-derived cells pre-treated by Ara-C (0.25 μM) and to determine the targeted killing ability of T cell subtypes induced by the diabody or ds-diabody combination with Ara-C both in vitro and in vivo. We also determined the levels of the cytokines that were released by activated CD4+ or CD8+ T cells during therapy. Result: Low-dose Ara-C enhanced CD80 and CD86 expression in nearly 50 % of specimens of B-ALL patient-derived cells. A combination of diabody or ds-diabody and Ara-C enhanced T cell against B-ALL cells in vitro and in vivo. Both CD8+ and CD4+ T cells were potently activated. Expression of CD25 and CD69 was augmented equally by CD4+ or CD8+ T cells. However, CD8+ T cells made the major contribution by redirecting target cell lysis in a granzyme B and perforin-dependent mechanism. CD4+ T cells played an important immunomodulatory role by secreting IL2. Consequently, IL3, IL6, TNFα, and IFNγ were also released by CD4+ or CD8+ T cells following diabody-mediated T cell activation. Conclusion: T cell therapy induced by diabody or ds-diabody combined with low dose of Ara-C was effective against cancer cell-lines and in clinical trials. In vivo, the ds-diabody was more efficient than its parent diabody due to its enhanced stability. [ABSTRACT FROM AUTHOR]

Published
2015
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2. Redirection of CD4+ and CD8+ T lymphocytes via an anti-CD3 × anti-CD19 bi-specific antibody combined with cytosine arabinoside and the efficient lysis of patient-derived B-ALL cells

Author

Yuqi Yang, Dongsheng Xiong, Ming Yang, Dongmei Fan, Xiaolong Zhang, Wei Li, Qing Zhang, Jianxiang Wang, and Yan Yan

Subjects
CD4-Positive T-Lymphocytes, Cytotoxicity, Immunologic, Cancer Research, CD3 Complex, Cancer immunotherapy, Mice, SCID, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Granzymes, Mice, Inbred NOD, Bi-specific antibody, Antibodies, Bispecific, Antineoplastic Combined Chemotherapy Protocols, Tumor Cells, Cultured, IL-2 receptor, Cells, Cultured, Gene Expression Regulation, Leukemic, Reverse Transcriptase Polymerase Chain Reaction, Cytarabine, B-ALL, Hematology, Flow Cytometry, Tumor Burden, medicine.anatomical_structure, Oncology, Cytokines, T cell, Antigens, CD19, Disulfide crosslinks, Antigen, Cell Line, Tumor, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, medicine, Animals, Humans, Molecular Biology, Diabody Anti-CD3, B cell, CD86, business.industry, Perforin, Research, Anti-CD19, Xenograft Model Antitumor Assays, Granzyme B, Immunology, Cancer research, business, CD8, CD80
Abstract

Background B-acute lymphoblastic leukemia (B-ALL) is derived from B cell progenitors. Recently, the development of appropriate combinations of chemotherapy and immunotherapy represents a promising approach for eliminating cancer. We previously constructed an anti-CD3 × anti-CD19 bi-specific antibody in a diabody configuration and its disulfide-stabilized format (ds-diabody). The combination of the diabody or ds-diabody and Ara-C was highly effective in enhancing the cytotoxicity of T cells against the CD19+ human leukemia cell-line, Nalm-6, both in vitro and in vivo. This study verified whether B-ALL patient-derived cells were sensitive to the diabody or ds-diabody and low-dosage Ara-C combination. Methods This study aimed to detect the B7 family members B7.1 (CD80) and B7.2 (CD86) that were expressed in B-ALL patient-derived cells pre-treated by Ara-C (0.25 μM) and to determine the targeted killing ability of T cell subtypes induced by the diabody or ds-diabody combination with Ara-C both in vitro and in vivo. We also determined the levels of the cytokines that were released by activated CD4+ or CD8+ T cells during therapy. Result Low-dose Ara-C enhanced CD80 and CD86 expression in nearly 50 % of specimens of B-ALL patient-derived cells. A combination of diabody or ds-diabody and Ara-C enhanced T cell against B-ALL cells in vitro and in vivo. Both CD8+ and CD4+ T cells were potently activated. Expression of CD25 and CD69 was augmented equally by CD4+ or CD8+ T cells. However, CD8+ T cells made the major contribution by redirecting target cell lysis in a granzyme B and perforin-dependent mechanism. CD4+ T cells played an important immunomodulatory role by secreting IL2. Consequently, IL3, IL6, TNFα, and IFNγ were also released by CD4+ or CD8+ T cells following diabody-mediated T cell activation. Conclusion T cell therapy induced by diabody or ds-diabody combined with low dose of Ara-C was effective against cancer cell-lines and in clinical trials. In vivo, the ds-diabody was more efficient than its parent diabody due to its enhanced stability.

Published
2015

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