AbstractTrop-2 has limited presence on normal tissues but is highly expressed in diverse epithelial cancers. (E1)-3s is a T-cell–redirecting trivalent bispecific antibody (bsAb), comprising an anti-CD3 scFv covalently linked to a stabilized dimer of a Trop-2–targeting Fab using Dock-and-Lock. We show for the first time that bsAb-mediated bidirectional trogocytosis occurs between target and T cells and involves immunologic synapses. We studied the effects of interferon-α (INFα) on (E1)-3s–mediated T-cell killing of human gastric and pancreatic cancer cell lines. T-cell activation, cytokine induction, and cytotoxicity were evaluated ex vivo using peripheral blood mononuclear cells (PBMC) or T cells with NCI-N87 gastric cancer as target cells. In vivo activity was assayed with NCI-N87 and Capan-1 (pancreatic) xenografts. In the presence of target cells and PBMCs, (E1)-3s did not cause excess cytokine production. When combined with (E1)-3s, peginterferonalfa-2a—which alone did not increase T-cell activation or raise cytokine levels over baseline—increased CD69 expression but did not significantly increase cytokine induction. (E1) 3s mediated a highly potent T-cell lysis of NCI-N87 target cells in vitro. Inclusion of peginterferonalfa-2a or a more potent form of INFα, 20*-2b, significantly potentiated the activity of (E1)-3s by more than 2.5- or 7-fold, respectively. In vivo, combining peginterferonalfa-2a with (E1)-3s delayed Capan-1 growth longer than each single agent. Similarly, combination therapy delayed tumor proliferation of NCI-N87 compared with (E1)-3s or peginterferonalfa-2a single-treatment groups. (E1)-3s effectively induced T-cell–mediated killing of Trop-2–expressing pancreatic and gastric cancers, which was enhanced with INFα. Mol Cancer Ther; 13(10); 2341–51. ©2014 AACR.

1989-08-01·Journal of biological response modifiers

Regression of MOPC 104E plasmacytoma with monoclonal anti-idiotype antibodies.

Article

作者: Hiramoto, N S ; Kodama, K ; Hiramoto, R N ; Ghanta, V K

We investigated the therapeutic effectiveness of monoclonal anti-idiotype (anti-M104E5) antibodies. Our in vitro studies show monoclonal anti-idiotype-specific antibody SJL18-1 showed a selective inhibitory property for MOPC 104E cells over two cross-reactive idiotype antibodies N-20-2 (IgM, IdX-M104E, and J558) and CD3-2 (IgG1, IdX-M104E, and J558). Based on these observations, we further examined their biological activities in vivo. Mice given 2 x 10(4) MOPC cells s.c. were treated with various doses of the antibodies i.v. on days 0, 7, 14, 21, and 28 after tumor transplantation. In the group treated with 100 micrograms of N-20-2 antibody, the antibody treatment prevented the growth of MOPC 104E in some of the mice. Treatment of tumor-bearing mice with SJL18-1 antibody (10 to 1,000 micrograms/mouse) did not provide any survival benefit. On the other hand, in mice treated with 50 micrograms of CD3-2 antibody, four of ten mice had regression of their palpable tumors. It is important to note that the least effective antibody (CD3-2) in vitro was the most effective in vivo, and the most effective antibody (SJL18-1) in vitro did not show any survival benefit. Preliminary data indicate that the most likely mechanism of in vivo regulation of MOPC 104E myeloma is by cytostatic lymphocytes.

100 项与 Trop-2 x CD3 Bi-Specific Antibody(iBio) 相关的药物交易

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