(E) -C-HDMAPP (ammonium salt)

Synthetic and natural alkyl phosphates, also known as phosphoantigens, stimulate the proliferation of γδ-T lymphocytes. Isopentenyl pyrophosphate, and related derivatives including (E) -hydroxy-dimethyl-allyl pyrophosphate ((E) -HDMAPP), are particularly effective activators of γδ-T cells. (E) -C-HDMAPP is the pyrophosphonate form of (E) -HDMAPP. The pyrophosphonate moiety in (E) -C-HDMAPP is much less susceptible to chemical or enzymatic hydrolysis than its pyrophosphate counterpart. As a result, (E) -C-HDMAPP is much more stable in solution and in vascular circulation. (E) -C-HDMAPP possesses comparable activity to (E) -HDMAPP, which is the most potent of the isoprenoid phosphoantigens. (E) -C-HDMAPP stimulates the synthesis of tumor necrosis factor (TNF-α) by γδ-T lymphocytes with an IC50 value of 0.91 nM. (E) -C-HDMAPP also significantly increases the number of circulating γδ-T cells in vivo, in cynomolgus monkeys.