Orchestrating immune check-point blockade for cancer immunotherapy in combinations.
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.
CIMA and Clinica Universidad de Navarra, Pamplona, Spain.
Jose Luis
JL
Perez-Gracia
CIMA and Clinica Universidad de Navarra, Pamplona, Spain.
Sara
S
Labiano
CIMA and Clinica Universidad de Navarra, Pamplona, Spain.
Maria E
ME
Rodriguez-Ruiz
CIMA and Clinica Universidad de Navarra, Pamplona, Spain.
Miguel F
MF
Sanmamed
CIMA and Clinica Universidad de Navarra, Pamplona, Spain. Electronic address: imelero@unav.es.
Ignacio
I
Melero
D000818:Animals; D060908:CTLA-4 Antigen / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D060908:CTLA-4 Antigen; D061026:Programmed Cell Death 1 Receptor