Does ipilimumab show an increased clinical benefit when combined in sequence with chemotherapy?
Ipilimumab is a fully human monoclonal antibody against cytotoxic T-cell lymphocyte antigen-4 (CTLA-4), which is not expressed by resting T cells and is only detected in activated T cells (1). CTLA-4 is known as a crucial negative regulator of the immune system, as it binds to B7 ligands (CD80/CD86) on antigen-presenting cells (APCs) with a high affinity and competes with costimulatory receptor CD28 on T cells for binding with B7 ligands (2). Ipilimumab works by blocking the binding of CTLA-4 to its ligands and augments T cell activation, leading to tumor regression (3). In contrast to conventional T (Tconv) cells, regulatory T (Treg) cells, which suppress aberrant immune responses, including the anti-tumor immune response, constitutively express CTLA-4 (4). Therefore, ipilimumab evokes effective tumor immunity by killing effector Treg cells or attenuating their suppressive activity.