Characterization of a mouse-human chimeric antibody to a cancer-associated antigen

R. Orlandi, M. Figini, A. Tomassetti, S. Canevari, M. I. Colnaghi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

In an attempt to obtain a therapeutic antibody, the murine monoclonal antibody (MAb) MBr1 (IgM,k), directed against human carcinomas, was converted in a mouse/human chimeric MAb of γ1 isotype. The chimeric MAb, γ1 CHI-MBr1, retains the ability to specifically bind tumor cells and tissues with no modification in its binding to the normal material tested. γ1 CHI-MBr1 recognizes mucins and high-molecular-weight glycoproteins carrying the antigenic determinant and stains a neutral glycolipid extracted from MCF-7 cells. The chimeric and the murine MBr1 efficiently cross-inhibit each other on the reference cell line MCF-7 and the calculated affinity constants amount to 3.8 x 107 and 1.7 x 108 M-1, respectively. The human constant region allows γ1 CHI-MBr1 to bind with the FcR on the human monocytic cell line U937 and to efficiently mediate antibody-dependent cellular cytotoxicity in the presence of human lymphocytes activated by IL2. In addition, γ1 CHI-MBr1, like the murine MBr1, mediates complement-dependent tumor cell lysis. Thus, by modelling a molecule with reduced size and increased functional characteristics, we have obtained a reagent which is more suitable for in vivo therapeutic approaches.

Original languageEnglish
Pages (from-to)588-593
Number of pages6
JournalInternational Journal of Cancer
Volume52
Issue number4
DOIs
Publication statusPublished - 1992

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Antigens
Antibodies
Monoclonal Antibodies
Neoplasms
Cell Line
Glycolipids
MCF-7 Cells
Mucins
Interleukin-2
Immunoglobulin M
Epitopes
Glycoproteins
Coloring Agents
Molecular Weight
Lymphocytes
Carcinoma
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Characterization of a mouse-human chimeric antibody to a cancer-associated antigen. / Orlandi, R.; Figini, M.; Tomassetti, A.; Canevari, S.; Colnaghi, M. I.

In: International Journal of Cancer, Vol. 52, No. 4, 1992, p. 588-593.

Research output: Contribution to journalArticle

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