3. Combination of CD39 with other immune checkpoints
The rapid development of flow cytometry in recent years has further
confirmed the expression of CD39 in tumor cells, particularly in
melanoma, lymphoma, and chronic lymphocytic leukemia (CLL) cell lines
[12, 13], in melanoma B16F10 mouse model and colorectal cancer Mc-38
mouse model, CD39-defective mice were resistant to tumor metastasis
[27, 52]. It has been documented that all cells expressing CD39
exhibit strong ATPase activity, which can be counterbalanced by CD39
inhibitors such as ARL-67156 and POM-1, by measuring the degradation of
eATP or release of free phosphate from cell culture supernatant.
Treatment with BY40, a CD39 blocking antibody currently under
preclinical development, reduced the inhibition of CD4+ and CD8+T cell
proliferation, which is induced by tumor tissue, and increased the
cytotoxicity that mediated by cytotoxic T lymphocyte (CTL) and NK
cell[14]. At present, many studies have proved that human CD39+CD8+
T cells exhibited consistent with draining dysfunction or phenotype gene
signature of T cell, including highly expressed inhibitory receptors
PD-1 and CTLA-4[53], thus targeted therapy of CD39 combined with
other immune binding sites has great significance in the therapy of
tumors. Currently, The main CD39 mAb used in clinical and research is
IPH5201, which blocks the hydrolysis of ATP by membrane and soluble
CD39, thus promoting DC maturation and macrophage activation[10];
BY40 has been reported to block membrane-associated, but insoluble,
human CD39 enzyme activity, but its clinical efficacy has not been
evaluated [10, 54]; POM1 is mainly used for experimental studies on
mice and cell lines [10].