Human monoclonal antibodies neutralizing cytomegalovirus (CMV) for prophylaxis of CMV disease: report of a phase I trial in bone marrow transplant recipients.
The safety and pharmacokinetics of the two neutralizing human IgG1 monoclonal antibodies to cytomegalovirus (CMV) SDZ 89-104 and 89-109 in bone marrow transplant (BMT) recipients was assessed in an open phase I trial. Thirteen patients, 8 seropositive and 5 seronegative for CMV, were treated with allogeneic or autologous bone marrow transplantation. SDZ 89-104 was given to 5 and SDZ 89-109 to 8 patients. Patients were divided into high- and low-dose groups. A fixed prestudy dose of 0.1 mg/kg was given 4 days before BMT. On days 3, 17, 31, 45, 59, and 73, patients were treated with either 0.5 or 2 mg/kg of the respective antibody. Results indicate that doses of 2 mg/kg of SDZ 89-104 or SDZ 89-109 in alternating weeks can be safely administered to BMT patients. Serum trough levels measured by antiidiotype ELISA were approximately 10 micrograms/ml after administration of 0.5 mg/kg and approximately 50 micrograms/ml after treatment with 2 mg/kg of SDZ 89-104 or SDZ 89-109. High serum levels defined by antiidiotype ELISA techniques closely paralleled increased neutralizing activity. Serum half-lives calculated from these data were approximately 6 days.
Aulitzky
W E
WE
Division of Clinical Immunobiology (Department of Internal Medicine), University Hospital Innsbruck, Austria.
Schulz
T F
TF
Tilg
H
H
Niederwieser
D
D
Larcher
K
K
Ostberg
L
L
Scriba
M
M
Martindale
J
J
Stern
A C
AC
Grass
P
P
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D004341:Drug Evaluation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006207:Half-Life; D006801:Humans; D007116:Immunization, Passive; D008297:Male; D008875:Middle Aged
D000911:Antibodies, Monoclonal