Historical evolution, overview, and therapeutic manipulation of co-stimulatory molecules

Table 5 Co-stimulatory molecule manipulation in various diseases

Disease	Therapeutic target	Manipulation	Outcome	Ref.
Brain metastases melanoma	PD-1 and CTLA-4	Blockade with mAbs (nivolumab + ipilimumab)	55% of treated patients reduced tumor size. 21% showed full response	[27]
Melanoma	PD-1	Blockade with mAbs (pembrolizumab or nivolumab)	19% of treated patient reduced tumor size	[28]
Melanoma	PD-1	Blockade with mAbs (pembrolizumab)	33% of treated patient reduce size tumor	[29]
Rheumatoid arthritis	CD80/CD86	Blockade with soluble receptor (abatacept)	Reduction in the disease index	[30]
Psoriatic arthritis	CD80/CD86	Blockade with soluble receptor (abatacept)	Musculoskeletal clinical improving	[31]
Sjögren syndrome	CD40	Blockade with recombinant antibody (CFZ533 or iscalimab)	Reduction in the disease index	[32]
Kidney graft	CD40	Blockade with recombinant antibody (CFZ533 or iscalimab)	Transplant success rate similar to tacrolimus treatment, but with a lower probability of adverse effects and infections	[33]

CTLA: Cytotoxic T lymphocyte antigen; PD-1: Programmed death-1.