Table 1. Development of pharmacological agents directed against immune-checkpoints signaling pathways ^{36 , 80} .

Target	Biological function	Antibodie	Clinical situation
CTLA-4	Inhibitory receptor	Ipilimumab	Approved by the FDA for melanoma. Phase IV trials for melanoma and metastatic renal cell cancer. Phase III trials for stomach / esophagus cancer, small cell and non-small cell lung cancer, renal carcinoma, pleural mesothelioma, metastatic squamous cell carcinoma of the head and neck, prostate cancer, ocular melanoma.
		Tremelimumab	Tested in phase III trials for melanoma, head and neck cancer, small and non-small cell lung cancer, urothelial cancer.
PD-1	Inhibitory receptor	Nivolumab	FDA approved for melanoma, renal carcinoma, non-small cell lung cancer. Phase IV trials for advanced metastatic renal carcinoma and metastatic melanoma. Phase III trials for small cell and non-small cell lung cancer, stomach/esophagus cancer, melanoma, mesothelioma, hepatocellular carcinoma, multiple myeloma, urothelial cancer, gastric cancer.
		Pembrolizumab	FDA approved for melanoma, non-small cell lung cancer. Phase III trials for melanoma and small and non-small cell lung cancer.
		Pidilizumab	Phase I/II trials for lymphoma, multiple myeloma, pancreatic cancer.
PD-L1	Programmed death-ligand 1	BMS-936559	Phase I trials for melanoma.
		Atezolizumab	Phase III trials for small cell and non-small cell lung cancer, triple negative breast cancer, urinary tract cancer, renal cancer, ovarian cancer, colorectal cancer, melanoma.
LAG3	Inhibitory receptor	IMP321	Phase I / II trials for breast adenocarcinoma, renal carcinoma, melanoma, pancreatic neoplasms.
B7-H3	Inhibitory ligand	Enoblituzumab	Phase I trials for various types of cancer.

CTLA-4: Cytotoxic T-Lymphocyte Antigen 4;

LAG3: Lymphocyte-activation gene 3;

PD-1: Programmed cell death protein 1;

PD-L1: Programmed death-ligand 1.