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Biotech / Medical : CLTR COULTER PHARMACEUTICAL

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To: Pseudo Biologist who wrote (394)	11/22/1999 11:12:00 PM
From: Bob L	Read Replies (2) of 666

TITLE: Preclinical evaluation of 90Y-labeled anti-CD20 monoclonal antibody for treatment of non-Hodgkin's lymphoma [In Process Citation] AUTHORS: Chinn PC; Leonard JE; Rosenberg J; Hanna N; Anderson DR AUTHOR AFFILIATION: IDEC Pharmaceuticals Inc., San Diego, CA 92121, USA. SOURCE: Int J Oncol 1999 Nov;15(5):1017-25 [MEDLINE record in process] CITATION IDS: PMID: 10536187 UI: 20007943 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 stable immunoconjugate (Zevalintrade mark) was prepared by reacting IDEC-2B8 with a derivative of diethylenetriaminepentaacetic acid, designated MX-DTPA, a chelator exhibiting high affinity and retention for 90Y. Zevalin exhibited antigen specificity, human tissue reactivity, and preclinical safety profile comparable to the native antibody. The conjugate radiolabeled with 90Y (90Y-Zevalin) or 111In (111In-Zevalin) exhibited excellent retention of immunoreactivity with radioincorporations >95%. The radiolabeled conjugates formulated in PBS containing human serum albumin were stable in vitro at 4 degrees C for 48 h as indicated by negligible loss of radioisotope and retention of binding to CD20+ cells. In vitro human serum stability studies at 37 degrees C with 90Y-Zevalin indicated that loss of 90Y from the conjugate was minimal, averaging 1% per day. Biodistribution studies in BALB/c mice confirmed the in vitro stability of 90Y-Zevalin and 111In- Zevalin. In particular, excellent in vivo retention of 90Y by the conjugate was demonstrated by minimal bone accumulation.

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