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In vitro: Ipilimumab, is a fully humanized IgG1k monoclonal antibody produced by recombinant DNA technology in a CHO mammalian cell expression system, binding with high affinity to the extracellular domain of human (and Cynomolgus monkey) CTLA-4, and acting as an inhibitor of its complex functions. This essentially results in T-cell activation and proliferation, and in lymphocyte infiltration leading to tumor cell death. However, the enhancement of T effector cell function, combined with the inhibition of CD4+ Treg and CD8+ suppressive cell types, are considered essential for mediating the full therapeutic effects of ipilimumab. Ipilimumab can improve ATC proliferation, enhance the BiAb-mediated tumor-specific cytotoxicity, and increase cytokine synthesis, while it attenuates Treg activity as shown by decreased level of IL-10 secretion and reduced Treg population. Ipilimumab and nivolumab treatments could collaboratively enhance effector and memory T cell responses without inappropriately activating naive T cells.
In vivo: Ipilimumab enhances antitumor immunity by inhibiting immunosuppressive activity of regulatory T cells (Treg).
MW: 148 kD.
| Cell Experiment | |
|---|---|
| Cell lines | PBMCs |
| Preparation method | Add ipilimumab at the initiation of ATC expansion cultures from healthy donors at various concentrations ranging from 0 to 50 μg/mL. ATC(activated T cells) are harvested on day 14, armed with EGFRBi or CD20Bi, and co-cultured at 25:1 E:T(effector:target) ratio for 18 hours with EGFR positive pancreatic cancer cell line (COLO356/FG) or 4 hours with CD20 positive Burkitt's lymphoma cell line (Daudi) for cytotoxicity assay. BiAb-mediated tumor specific cytotoxicity is measured by 51Cr release assay. |
| Concentrations | 0, 0.5, 5.0, and 50 μg/mL |
| Incubation time | 14 days |
| Animal Experiment | |
|---|---|
| Animal models | Purpose-bred cynomolgus monkeys |
| Formulation | Saline |
| Dosages | 3 mg/kg or 10 mg/kg |
| Administration | i.v. |
| Molecular Weight | 148631.92 |
| Formula | C6742H9972N1732O2004S40 |
| CAS Number | 477202-00-9 |
| Storage | -80°C for long term |
[5] Robert C, et al. N Engl J Med. Pembrolizumab versus Ipilimumab in Advanced Melanoma.
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