| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3345816 | Current Opinion in Immunology | 2014 | 9 Pages |
•Immunity against cancer is negatively regulated by lymphocyte surface receptors.•Cellular immunity against cancer can be unleashed by mAbs acting on such receptors.•Clinical trial evidence has shown efficacy with ipilimumab (a CTLA-4-blocking mAb).•Blockade of the PD-1/PD-L1 axis shows very promising activity in cancer patients.•Combination strategies under development attain synergistic effects.
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.
