NCIt definition : An Fc-optimized humanized immunoglobulin (Ig) G1 monoclonal antibody (MoAb) directed
against the inducible T-cell co-stimulator (ICOS, CD278), with potential immune checkpoint
inhibitory and antineoplastic activities. Upon administration, anti-ICOS MoAb MEDI-570
targets and binds to ICOS expressed on tumor infiltrating CD4-positive T-cells. This
prevents the interaction between ICOS-positive T-cells and plasmacytoid dendritic
cells (pDCs), which express the ICOS ligand (ICOSL). Blocking ICOS activation prevents
the pDC-induced proliferation and accumulation of regulatory ICOS-positive T-cells
(ICOS Tregs) and inhibits interleukin-10 (IL-10) secretion by CD4 infiltrating T-cells.
This may abrogate Treg-mediated immune suppression and may enhance cytotoxic T-lymphocyte
(CTL)-mediated immune responses against tumor cells. Fc optimization enhances antibody-dependent
cellular cytotoxicity (ADCC). ICOS, a T-cell specific, CD28-superfamily costimulatory
molecule and immune checkpoint protein, plays a key role in the proliferation and
activation of T-cells. It is normally expressed on both activated CD4 T-cells, which
is a subset of memory T-cells (Tm), and follicular helper T-cells (Tfh). ICOS is highly
expressed on Tregs infiltrating various tumors and its expression is associated with
a poor prognosis; ICOS-positive Tregs play a key role in immune suppression and tumor
immune evasion.;