Preclinical evaluation of Y-90-labeled anti-CD20 monoclonal antibody for treatment of non-Hodgkin's lymphoma

Citation
Pc. Chinn et al., Preclinical evaluation of Y-90-labeled anti-CD20 monoclonal antibody for treatment of non-Hodgkin's lymphoma, INT J ONCOL, 15(5), 1999, pp. 1017-1025
Citations number
34
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF ONCOLOGY
ISSN journal
10196439 → ACNP
Volume
15
Issue
5
Year of publication
1999
Pages
1017 - 1025
Database
ISI
SICI code
1019-6439(199911)15:5<1017:PEOYAM>2.0.ZU;2-5
Abstract
A high-affinity IgG1 kappa murine monoclonal anti-CD20 antibody (IDEC-2B8) was developed for radioimmunotherapy of non-Hodgkin's B-cell lymphoma. A st able immunoconjugate (Zevalin(TM)) was prepared by reacting IDEC-2B8 with a derivative of diethylenetriaminepentaacetic acid, designated MX-DTPA, a ch elator exhibiting high affinity and retention for Y-90. Zevalin exhibited a ntigen specificity, human tissue reactivity, and preclinical safety profile comparable to the native antibody. The conjugate radiolabeled with 90Y (Y- 90-Zevalin) or In-111 (In-111-Zevalin) exhibited excellent retention of imm unoreactivity with radioincorporations >95%. The radiolabeled conjugates fo rmulated in PBS containing human serum albumin were stable in vitro at 4 de grees C for 48 h as indicated by negligible loss of radioisotope and retent ion of binding to CD20(+) cells. In vitro, human serum stability studies at 37 degrees C with Y-90-Zevalin indicated that loss of 90Y from the conjuga te was minimal, averaging 1% per day. Biodistribution studies in BALB/c mic e confirmed the in vitro stability of Y-90-Zevalin and In-111-Zevalin. In p articular, excellent in vivo retention of 90Y by the conjugate was demonstr ated by minimal bone accumulation (less than or equal to 3% of the injected dose over three days). Radiation dose estimates to normal organs calculate d from mouse biodistribution studies with Y-90-Zevalin were comparable to t hose determined in a phase I/II clinical trial and below generally accepted safe radiation levels. Studies in athymic mice bearing CD20(+) tumors demo nstrated that In-111-Zevalin accumulated in the tumors preferentially compa red with normal organs. Y-90-Zevalin is currently being evaluated in phase III clinical trials for treatment of relapsed or refractory low-grade, foll icular or transformed B-cell non-Hodgkin's lymphoma.