Safety, tolerability, and pharmacology of AB928, a novel dual adenosine receptor antagonist, in a randomized, phase 1 study in healthy volunteers

• Published in: Investigational new drugs Vol. 37; no. 4; pp. 711 - 721
• Main Authors: Seitz, Lisa, Jin, Lixia, Leleti, Manmohan, Ashok, Devika, Jeffrey, Jenna, Rieger, Aimee, Tiessen, Renger G., Arold, Gerhard, Tan, Joanne B. L., Powers, Jay P., Walters, Matthew J., Karakunnel, Joyson
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2019; Springer Nature B.V
• Subjects: Absorption; Adenosine; Administration, Oral; Adolescent; Adult; Antitumor activity; Cancer; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - metabolism; Cyclic AMP; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - metabolism; Double-Blind Method; Female; Food-Drug Interactions; Healthy Volunteers; Humans; Immune response; Immune system; Immunotherapy; Inhibition; Iron; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Parameter identification; Parameter sensitivity; Pharmacodynamics; Pharmacokinetics; Pharmacology; Pharmacology/Toxicology; Phase I Studies; Phosphorylation; Plasma levels; Proteins; Purinergic P1 Receptor Antagonists - administration & dosage; Purinergic P1 Receptor Antagonists - blood; Purinergic P1 Receptor Antagonists - pharmacokinetics; Randomization; Receptors; Safety; Studies; Young Adult; Adenosine signaling; Oncology; Adenosine receptor antagonist; Healthy volunteers; AB928; Immunotherapy

Summary Adenosine suppresses antitumor immune responses via A 2a and A 2b receptors expressed on intratumoral immune cells. This effect is mediated by increased cyclic adenosine 5′-monophosphate (AMP) levels and phosphorylation of cyclic AMP response element binding protein (CREB). We conducted a ph...