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- W2267066412 abstract "e13107 Background: Several mechanisms account for the ability of the immune system to mount protective immunity while maintaining self-tolerance. At the single-cell level, the integration of signals delivered by activating and inhibitory receptors determines whether immunity will be initiated or suppressed. Immunoglobulin-like transcripts (ILTs) are polymorphic receptors found on the surface of human and nonhuman primate leukocytes and have the potential for either activating or inhibitory function. ILT5, an inhibitory member of the ILT family with unknown function, is predominantly expressed on antigen-presenting cells (APCs), such as dendritic cells and monocytes. Here, we report on the potent immunoregulatory properties of TRX585, a novel monoclonal antibody (Mab) that targets ILT5. Methods: The immunoregulatory potential of TRX585 was investigated in vitro using mixed leukocyte cultures. T-cell proliferation and activation were monitored using 3H-thymidine incorporation or flow cytometry. Cytotoxicity and Fas ligand release by T cells were quantified by flow cytometry and ELISA, respectively. Results: Upon exposure to APCs with cell-bound TRX585, human T cells proliferated in a T-cell receptor (TCR)-independent manner, upregulated the innate immune receptor, NKG2D, and sustained elevated levels of NKG2D under conditions that normally trigger its internalization. In addition, T cells showed increased responsiveness to subsequent TCR stimulation, secreted high levels of Fas ligand, and acquired cytotoxic potential. Both CD4 and CD8 T cells that were isolated from TRX585-containing cultures efficiently killed a variety of human tumor cell lines. This was shown to be major histocompatibility class I antigen- and Fas ligand-dependent. Conclusions: Our studies uncovered a novel pathway, involving the ILT5 receptor, by which human T cells can be potently activated, become cytotoxic, and acquire an innate immune receptor known to have an important role in preventing the dissemination of tumor cells and viruses. Because TRX585 activates this pathway, it may be useful in the treatment of viral infections and/or malignancies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Tolerx, Inc. Tolerx, Inc." @default.
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- W2267066412 date "2010-05-20" @default.
- W2267066412 modified "2023-09-24" @default.
- W2267066412 title "Immunoregulatory properties of TRX585, a novel monoclonal antibody specific for immunoglobulin-like transcript 5." @default.
- W2267066412 doi "https://doi.org/10.1200/jco.2010.28.15_suppl.e13107" @default.
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