Kiniksa is progressing its preclinical activities with KPL-404, a monoclonal antibody inhibitor of the CD40 co-stimulatory
receptor in diseases characterized by T-cell-dependent, B-cell-mediated pathology.
The AVA-001 candidate uses the 4-1BB co-stimulatory
signaling pathway, conferring strong anti-cancer activity as demonstrated during the pre-clinical study.
Among other pipeline programs, CBI has discovered and is developing an advanced approach to CAR-T/antibody constructs utilising the company's novel next generation co-stimulatory
and co-signaling domains.
Ligation of CD137 induces a co-stimulatory
signal on activated CD8+ T cells and natural killer (NK) cells, resulting in proliferation, increased pro-inflammatory cytokine secretion and cytolytic function, revealed the company.
"We have identified one of metabolism's most popular hormones, specifically the insulin signalling pathway, as a novel 'co-stimulatory
' driver of immune system function," said Assistant Professor, Dr Dan Winer.
ATOR-1015 binds to the checkpoint receptor CTLA-4 and the co-stimulatory
B cells require a co-stimulatory
signal together with antigen recognition for B cell activation.
Ito et al., "Allogeneic bone marrow transplantation with co-stimulatory
blockade induces macrochimerism and tolerance without cytoreductive host treatment," Nature Medicine, vol.
In response to sensing the danger signals by PRRs such as toll-like receptors, APCs produce co-stimulatory
molecules and polarizing cytokines that promote adaptive immunity into the best responses against the danger signals.
The balance of co-stimulatory
and co-inhibitory molecules, which are expressed on T-cells control the immunological response, is crucial in the adaptive immunosuppression induced by sepsis.[sup], Upregulated expression of co-inhibitory receptors on T-cell surface inhibit T-cell function by inducing cell exhaustion and apoptosis.
Engagement of T cells requires two signals: antigen recognition through the T cell receptor (TCR) and major histocompatibility complex (MHC); and co-stimulatory
or co-inhibitory signals.
MHC associated antigen presentation and interaction of co-stimulatory
molecules particularly T-cell surface specific glycoprotein CD28 with T-cell activation antigens CD80 and CD86 that are expressed on antigen presenting cells15.