Development of XPA067.06, a potent high affinity human anti-gastrin monoclonal antibody.
The peptide hormone gastrin is a key factor in regulation of gastric acid secretion. It has also been implicated in the development or maintenance of various types of cancer, such as pancreatic and stomach carcinoma. Inhibition of gastrin activity has potential for therapeutic use as a suppressor of acid secretion as well as an inhibitor of gastrin-responsive tumors. XPA067.06 is an affinity matured, 30 pM fully human anti-gastrin monoclonal antibody that was generated. The antibody was tested in a mouse gastric pH model to determine its effect on acid secretion. In this model, animals were treated with human gastrin, XPA067.06, and H2R or M1 receptor antagonists. Gastric fluid was collected and acid output was measured as a function of pH. XPA067.06 was shown to significantly inhibit gastrin-17-stimulated acid output for at least 48h. These results demonstrate that XPA067.06 effectively binds and neutralizes human gastrin-17 in vivo with rapid onset and prolonged duration of efficacy.
Hsu
Ssucheng J
SJ
Preclinical Research & Development, XOMA (US) LLC, 2910 Seventh Street, Berkeley, CA 94710, USA. hsu@xoma.com
Patel
Amita
A
Larsen
Paul D
PD
Bohmann
David J
DJ
Bauer
Robert J
RJ
Ma
Jeremy K
JK
Masat
Linda
L
Roell
Marina
M
Babuka
Susan J
SJ
Hansen
Rhonda K
RK
White
Mark
M
Haak-Frendscho
Mary
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000494:pharmacology; D000915:Antibody Affinity / Q000502:physiology*; D001666:Binding Sites, Antibody; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics; D005744:Gastric Acid / Q000378:metabolism; D005755:Gastrins / Q000037:antagonists & inhibitors / Q000276:immunology*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D051379:Mice; D019151:Peptide Library; D011993:Recombinant Fusion Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D005755:Gastrins; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D019151:Peptide Library; D011993:Recombinant Fusion Proteins; C013550:gastrin 17