Orchestrating immune check-point blockade for cancer immunotherapy in combinations

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• 作者：Jose Luis Perez-Gracia ; Sara Labiano ; Maria E Rodriguez-Ruiz ; Miguel F Sanmamed ; Ignacio Melero ^{imelero@unav.es" class="auth_mail}
• 刊名：Current Opinion in Immunology
• 出版年：April, 2014
• 年：2014
• 卷：27
• 期：Complete
• 页码：89-97
• 全文大小：825 K

文摘

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 鈥?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.