Ipilimumab (MDX-010)

Biological Activity

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 is shown in phase III clinical trials to have a survival benefit in metastatic melanoma that is durable in 10% to 20% of patients. Conceivably, the main adverse effects of ipilimumab are autoimmunein nature. Ipilimumab enhances antitumor immunity by inhibiting immunosuppressive activity of regulatory T cells (Treg).

References:
[1].Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial.
Antonia SJ, et al. Lancet Oncol. 2016 Jul;17(7):883-895. PMID: 27269741.
[2].Pembrolizumab versus Ipilimumab in Advanced Melanoma.
Robert C, et al. N Engl J Med. 2015 Jun 25;372(26):2521-32. PMID: 25891173.