Therapeutic potential of chimeric amyloid-reactive monoclonal antibody 11-1F4

Alan Solomon, Deborah T. Weiss, Jonathan Wall

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Purpose: We had previously reported that certain of our murine (m) antihuman light chain monoclonal antibodies (mAbs) recognized an epitope common to AL and other types of amyloid fibrils. On the basis of this evidence, one such antibody, 11-1F4, was administered to mice bearing AL amyloidomas induced by s.c. injection of human AL extracts. The mAb bound to the amyloid and initiated an Fc-mediated cellular inflammatory response that led to rapid reduction in the tumor masses. To develop this reagent for clinical use, the 11-1F4 mAb was chimerized and its activity compared with that of the unmodified antibody. Experimental Design: The chimeric (c) 11-1F4 mAb was produced in CHOdhfr-stable mammalian cell lines that had been transfected with a supervector DNA encoding the mouse 11-1F4 heavy and light chain variable regions (VH, VL) and human heavy and light chain constant regions (CH, CL). The antibody products were analyzed for their fibril binding activity and ability to effect amyloidolysis in two in vivo experimental models. Results: The capability of the c11-1F4 mAb to interact with amyloid was demonstrated in vitro. Administration of this reagent into mice bearing human AL tumors or those with systemic AA deposits resulted in marked reduction in amyloid burden with no evidence of toxicity in the animals. Conclusions: These results have led to the decision to produce GMP-grade cl 1-1F4 for a Phase I/II clinical trial in patients with primary (AL) amyloidosis where the effectiveness of the reagent could be determined. The use of amyloidreactive antibodies would represent a novel approach in the treatment of individuals with this invariably fatal disorder.

Original languageEnglish (US)
JournalClinical Cancer Research
Volume9
Issue number10 II
StatePublished - Oct 1 2003

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Amyloid
Monoclonal Antibodies
Antibodies
Light
Phase II Clinical Trials
Clinical Trials, Phase I
Therapeutics
Epitopes
Neoplasms
Research Design
Theoretical Models
Cell Line
Injections
DNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Therapeutic potential of chimeric amyloid-reactive monoclonal antibody 11-1F4. / Solomon, Alan; Weiss, Deborah T.; Wall, Jonathan.

In: Clinical Cancer Research, Vol. 9, No. 10 II, 01.10.2003.

Research output: Contribution to journalArticle

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