Expression and characterization of a mouse/human chimeric antibody specific for EGF receptor

Ferrer, Cristina Suárez; Anastasi, Anna Maria; Massimo, A. M. Di; Bullo, Angela; Loreto, Mario Di; Raucci, Giuseppe; Pacilli, A.; Rotondaro, Luigi; Mauro, Sandro; Mele, Antonio; Santis, Rita De

doi:10.1016/s0168-1656(96)01625-2

Cited by 3 publications

(3 citation statements)

References 25 publications

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“…In addition to ocymoidine and pyramidatine, other RIPs are in preparation in our laboratory in order to overcome the immunogenicity problems related to therapeutic regimens requiring multiple administrations. Moreover, a humanized version of MintS antibody has been obtained recently in our laboratory showing substantially the same properties of parental MAb (Ferrer et al, 1997).…”

Section: Discussionmentioning

confidence: 82%

Immunoconjugates made of an anti-EGF receptor monoclonal antibody and type 1 ribosome-inactivating proteins from Saponaria ocymoides or Vaccaria pyramidata

Massimo

Loreto²,

Pacilli³

et al. 1997

Br J Cancer

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Summary The present paper describes two immunoconjugates consisting of an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb), named Mint5, covalently linked to the type 1 ribosome-inactivating proteins (RlPs) ocymoidine (Ocy) and pyramidatine (Pyra) from Saponaria ocymoides and Vaccaria pyramidata respectively. Both antibody and toxins are shown to retain their respective biological properties upon chemical conjugation. The immunoconjugates exert specific inhibition of EGFR expressing target cell proliferation and protein synthesis in in vitro assays and also inhibit the growth of grafted human tumour cells in nude mice.Keywords: immunoconjugate; anti-epidermal growth factor receptor; ocymoidine; pyramidatineThe clinical use of immunotoxins for the treatment of cancer is currently under evaluation worldwide. The therapeutic potentiality of immunotoxins and preclinical and clinical results over the last 20 years have been reviewed recently (Thrush et al, 1996), indicating that, although immunotoxins seem promising for systemic therapy of haematological malignancies, a number of different problems still need to be solved, especially for the treatment of solid tumours. In particular, the refining of dose regimen and administration route, the combination with chemotherapy and the reduction of immunogenicity are the major goals of future research. In this paper, we describe the preparation of two new immunoconjugates made of an anti-epidermal growth factor receptor monoclonal antibody, named MintS, chemically linked to either ocymoidine or pyramidatine, toxins from Saponaria ocymoides and Vaccaria pyramidata respectively.The epidermal growth factor (EGF) and its receptor play a critical role in the growth and regulation of many normal and malignant cell types. EGFR overexpression is a common feature in most carcinomas and correlates with poor prognosis (Fox et al, 1994).The potential value of EGFR as a target for the diagnosis and therapy of human tumours has been recognized for several years, and the use of anti-EGFR monoclonal antibodies may provide therapeutic tools in the treatment of tumours overexpressing the receptor (Ennis et al, 1991).Moreover, immunoconjugates of EGFR-specific monoclonal antibodies to either gelonin (Ozawa et al, 1989) or ricin A chain (Masui et al, 1989) were shown to reduce the growth of human tumour cells transplanted into athymic mice.

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Section: Discussionmentioning

confidence: 82%

Immunoconjugates made of an anti-EGF receptor monoclonal antibody and type 1 ribosome-inactivating proteins from Saponaria ocymoides or Vaccaria pyramidata

Massimo

Loreto²,

Pacilli³

et al. 1997

Br J Cancer

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show abstract

“…Hybridomas were generated by cell fusion of spleen cells from A431-immunized mice and SP2/0 myeloma cells following the reported method (Ferrer et al, 1996;Kim et al, 2001;Song et al, 2008). The culture supernatants of hybridomas were screened by ELISA for sEGFR binding activity.…”

Section: Generation Of Mab Against Human Egfrmentioning

confidence: 99%

“…Here we report a novel anti-EGFR mAb, A13, generated by immunizing mice with human A431 cervical carcinoma cells that overexpress EGFR (Parker et al, 1984;Ferrer et al, 1996). mAb A13 specifically bound to soluble EGFR (sEGFR) and various sets of EGFRexpressing tumor cells and inhibited EGFR activation and colony formation of tumor cells, by competitive binding to EGFR with EGF, but not with cetuximab.…”

mentioning

confidence: 99%