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Titolo:
Production and functional characterization of two mouse/human chimeric antibodies with specificity for the tumor-associated Tn-antigen
Autore:
Oppezzo, P; Osinaga, E; Tello, D; Bay, S; Cantacuzene, D; Irigoin, F; Ferreira, A; Roseto, A; Cayota, A; Alzari, P; Pritsch, O;
Indirizzi:
Fac Med, Dept Bioquim, Montevideo 11800, Uruguay Fac Med Montevideo Uruguay 11800 Dept Bioquim, Montevideo 11800, Uruguay Fac Quim, Ctr Inmunol, Montevideo, Uruguay Fac Quim Montevideo UruguayFac Quim, Ctr Inmunol, Montevideo, Uruguay Inst Pasteur, Unite Biochim Struct, Paris, France Inst Pasteur Paris France Pasteur, Unite Biochim Struct, Paris, France Inst Pasteur, Unite Chim Organ, F-75724 Paris, France Inst Pasteur ParisFrance F-75724 nite Chim Organ, F-75724 Paris, France Univ Technol Compiegne, DICA, F-60206 Compiegne, France Univ Technol Compiegne Compiegne France F-60206 -60206 Compiegne, France
Titolo Testata:
HYBRIDOMA
fascicolo: 3, volume: 19, anno: 2000,
pagine: 229 - 239
SICI:
0272-457X(200006)19:3<229:PAFCOT>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
MONOCLONAL-ANTIBODY; BREAST-CARCINOMA; CARBOHYDRATE ANTIGENS; SEROUS EFFUSIONS; CANCER-THERAPY; CELL-LINE; PHARMACOKINETICS; EXPRESSION; BINDING; CHAIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Pritsch, O Fac Med, Dept Bioquim, Avda Gen Flores 2125, Montevideo 11800, Uruguay Fac Med Avda Gen Flores 2125 Montevideo Uruguay 11800 Uruguay
Citazione:
P. Oppezzo et al., "Production and functional characterization of two mouse/human chimeric antibodies with specificity for the tumor-associated Tn-antigen", HYBRIDOMA, 19(3), 2000, pp. 229-239

Abstract

In this work, we have constructed two functional mouse/human chimeric antibodies (IgM kappa and IgG(1)kappa isotypes) by inserting genomic DNA fragments encoding VH and VK variable regions of the murine monoclonal antibody IgM kappa-83D4 into mammalian expression vectors containing human mu, gamma 1, and kappa constant exons, and by transfecting them into the nonsecretingmouse myeloma X-63 cell line. In previous works, we have demonstrated that83D4 murine mAb reacts with Tn determinant (GalNAc alpha-O-Ser/Thr) expressed in 90% of breast, ovary, and colon carcinomas. Both expressed chimeric antibodies were purified from the transfected cell line supernatant by affinity chromatography, and their reactivities against Tn antigen were confirmed by ELISA on asialo ovine submaxilar mucin and immunofluorescence studieson MCF-7 breast carcinoma cell line. We have demonstrated by gel filtration chromatography, that the principal secreted forms were monomers for IgG(1)kappa and pentamers for IgM kappa, The binding affinities of these chimeric antibodies against synthetic Tn glycopeptides, were evaluated by surface plasmon resonance showing an affinity constant similar to that of 83D4 native antibody for IgM kappa and a lower affinity constant for IgG(1)kappa chimeric antibody, On the other hand, the replacement of mouse C regions with human C regions confers both chimeric antibodies the ability to activate human complement. These mouse/human chimeric antibodies should be much less immunogenic and could play an important role in the lysis of tumor cell expressing Tn-antigen. Therefore, these anti-Tn chimeric antibodies could be considered as potential tools for human in vivo studies.

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Documento generato il 01/04/20 alle ore 20:47:31