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Titolo:
PLASMA PHARMACOKINETICS AND BIOLOGICAL-ACTIVITY OF A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 NEUTRALIZING HUMAN MONOCLONAL-ANTIBODY, F105, IN CYNOMOLGUS MONKEYS
Autore:
CAVACINI LA; POWER J; EMES CL; MACE K; TREACY G; POSNER MR;
Indirizzi:
HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT MED,RES CRI BSMT010,185 PILGRIM RD BOSTON MA 02215 CENTOCOR INC MALVERN PA 19355
Titolo Testata:
Journal of immunotherapy with emphasis on tumor immunology
fascicolo: 4, volume: 15, anno: 1994,
pagine: 251 - 256
SICI:
1067-5582(1994)15:4<251:PPABOA>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT SOLUBLE CD4; PHASE-I TRIAL; IMMUNE-RESPONSE; HIV-1 GP120; CONFORMATIONAL EPITOPE; ENVELOPE GLYCOPROTEIN; BINDING-SITE; INFECTION; AFFINITY; PROTEIN;
Keywords:
HUMAN MONOCLONAL ANTIBODIES; HIV ANTIBODIES; SEROTHERAPY; ADOPTIVE IMMUNOTHERAPY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
48
Recensione:
Indirizzi per estratti:
Citazione:
L.A. Cavacini et al., "PLASMA PHARMACOKINETICS AND BIOLOGICAL-ACTIVITY OF A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 NEUTRALIZING HUMAN MONOCLONAL-ANTIBODY, F105, IN CYNOMOLGUS MONKEYS", Journal of immunotherapy with emphasis on tumor immunology, 15(4), 1994, pp. 251-256

Abstract

The IgG1 kappa human monoclonal antibody (HMab), F105 reacts with a discontinuous epitope on the CD4 binding site (CD4BS) of human immunodeficiency virus type 1 (HIV-1)/gp120 and has broad neutralizing activity. F105 HMab (60 mg/kg bolus) was administered intravenously to four monkeys and serum was collected at intervals to determine pharmacokinetics in a primate model. Average serum F105 concentrations, as determined by enzyme-linked immunosorbent assay, were analyzed with MINSQ software using a two-compartment, first-order model. The half-life for thealpha phase of the distribution curve is 6.7 h and for the beta elimination phase, 9.6 days. The volume of distribution is 0.65 L/kg and the rate of clearance 2 ml/kg/h. Serum levels of 1.3-1.6 mg/ml of F105 were maintained for 24 h. When monkey serum from day 15 postdose was tested, total serum F105 was 230 +/- 79 mu g/ml and was immunoreactive with cells infected with the MN and IIIB strains of HIV-1 as determinedby flow cytometry. Binding activity was identical to that obtained with stock F105 HMab. identical neutralizing activity between the injected and uninjected antibody was also observed. Thus, serum neutralizingtiters (90%) of 1:2000 at peak and 1:30 at day 15 postdose for MN virus were observed. These data indicate that high in vivo levels of HMabF105 can be attained by single bolus administration with full retention of biological activity. Of importance, levels of antibody necessaryfor effective neutralization can be achieved and maintained.

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Documento generato il 30/11/20 alle ore 14:50:05