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Orchestrating immune check-point blockade for cancer immunotherapy in combinations

2014; Elsevier BV; Volume: 27; Linguagem: Inglês

10.1016/j.coi.2014.01.002

1879-0372

Jose Luis Pérez‐Gracia, Sara Labiano, María E. Rodríguez-Ruiz, Miguel F. Sanmamed, Ignacio Melero,

CAR-T cell therapy research

Inhibitory receptors on immune system cells respond to membrane-bound and soluble ligands to abort or mitigate the intensity of immune responses by raising thresholds of activation, halting proliferation, favoring apoptosis or inhibiting/deviating effector function differentiation. Such evolutionarily selected inhibitory mechanisms are termed check-points and therefore check-point inhibitors empower any ongoing anti-cancer immune response that might have been too weak or exhausted. Monoclonal antibodies (mAb) interfering with CTLA-4-CD80/86, PD-1 - PD-L1, TIM-3-GAL9 and LAG3-MHC-II belong to this category of check-point inhibitors. The anti-CTLA-4 mAb ipilimumab has been approved for metastatic melanoma. Anti-PD-1 and anti-PD-L1 mAbs have shown extremely encouraging clinical activity. The potential of combination strategies with these agents has recently been highlighted by clinical observations on CTLA-4+PD-1 combined blockade in melanoma patients.