A novel antibody targeting the ligand binding domain of the thromboxane A2 receptor exhibits antithrombotic properties in vivo

Investigation of a Thromboxane A 2 Receptor–Based Vaccine for Managing Thrombogenesis

“…In light of our previous findings that treatment with the C‐EL2Ab inhibits platelet aggregation,19, 47 we decided to examine whether immunizations of live animals with the C‐EL2 peptide would also translate into inhibition of platelet aggregation. Indeed, it was found that vaccination with C‐EL2 (35 μg), unlike C‐EL2r or KLH, resulted in inhibition of 1 μmol/L U46619‐stimulated platelet aggregation (Figure 2A), whereas it had no effects on that induced by either ADP (5 μmol/L; Figure 2B) or TRAP4 (80 μmol/L; Figure 2C).…”

“…These studies were performed, as described previously 19, 42, 44. Briefly, vaccinated mice (C‐EL2, C‐EL2r, and KLH) were anesthetized with isoflurane.…”

“…Hemostasis in the vaccinated mice (C‐EL2, C‐EL2r, and KLH) was examined using the tail transection technique 19, 42, 44. Briefly, mice were anesthetized with isoflurane and placed on a 37°C homeothermic blanket, and their tails were transected 5 mm from the tip.…”

“…To this end, TPR's clear role in normal hemostasis is supported by the finding that “patients” have a bleeding disorder as a result of a point mutation in the receptor protein 14, 15, 16. On the other hand, upregulated signaling through TPR has been implicated in the pathogenesis of multiple cardiovascular and thrombosis‐based diseases 17, 18, 19, 20. Consistent with this concept are clinical findings indicating that inhibition of platelet TXA 2 production provides therapy for thromboembolic diseases,21, 22, 23 which is the underlying rationale for the use of aspirin in such diseases 24, 25…”

TxA 2 Receptor‐Based Vaccination: A Novel Potential Therapeutic Approach to Limit Thrombosis

“…Taking these studies further, authors have previously characterized C‐EL2Ab (antibody against C‐EL2 domain) and showed that the antibody selectively blocks TPR‐mediated platelet aggregation 11. Along the same lines, they have characterized C‐EL2Ab in vivo and concluded that the antibody protects mice against the development of occlusive arterial thrombosis without increasing the risk of bleeding 12. These key studies led authors to develop a vaccine against TPR that could potentially be used in humans.…”