Abstract
When the cytotoxic T-lymphocyte-associated protein (CTLA)-4 molecule, present on the surface of a lymphocyte after immune cell activation, binds B7 surface molecules, T-lymphocyte anergy occurs, resulting in cell proliferation and inhibition of IL-2 secretion. Treatment with the anti-CTLA-4 monoclonal antibody ipilimumab (MDX-010) seems to prevent this anergy and permits specific T-lymphocyte activation against tumor antigens. Two Phase I trials on metastatic melanoma have been conducted using doses ranging from 3 to 20 mg/kg, followed by several Phase II trials. Although immune-related adverse events were reported in most of the clinical trials, these were generally manageable with systemic steroids or symptomatic treatments, and anti-tumor efficacy did not appear to be affected. Durable objective response rates were obtained in 4.6–15% of patients, with a further increment in late responses after long-term stable disease or after initial progression. Early and late responses, or stabilizations that are preceded by apparent progressive disease, would seem to indicate that new efficacy criteria are needed to describe the clinical benefit of ipilimumab.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.