Growth inhibition of xenotransplanted human carcinomas by a monoclonal antibody directed against the epidermal growth factor receptor

Hg, Schnürch; Stegmüller, M.; Vering, A.; Beckmann, MW

doi:10.1016/0959-8049(94)90425-1

Cited by 21 publications

(10 citation statements)

References 13 publications

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“…Moreover, the 2 cell lines were positive for staining with an anti-TGFa MAb by flow-cytometry analysis (data not shown). The EGFR/TGFa autocrine loop in A431 cells is well documented (Van d e Vijver et al, 1991), whereas previous data indicating that IGROVl EGF-free conditioned medium does not contain secreted forms of TGFa (Stromberg et al, 1992) are in zpparent contrast with our findings. However, an unprocessed, membrane-associated TGFa precursor was found at the cell surface of some tumor cell lines (Brachmann et al, 1989).…”

Section: Discussioncontrasting

confidence: 85%

Anti‐tumor efficacy of an anti‐epidermal‐growth‐factor‐ receptor monoclonal antibody and its F(ab′)₂ fragment against high‐ and low‐egfr‐expressing carcinomas in nude mice

Tosi

Valota

Negri

et al. 1995

Intl Journal of Cancer

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Monoclonal antibody (MAb) MINT5 specifically detects the epidermal-growth-factor receptor (EGFR). In vitro analyses of intact MINT5 (IgG1) and its F(ab')2 fragment indicated that both forms of the MAb inhibited binding of 125I-mEGF to EGFR, induced receptor internalization and blocked EGF-induced EGFR tyrosine-kinase activation in A431 cells. Both forms of the MAb also inhibited to the same extent the proliferation of the carcinoma cell lines A431 and IGROVI, despite the difference in EGFR levels on the cells. The detection of TGF alpha mRNA and the inhibition of cell growth in EGF-free conditions by anti-EGFR MAb indicated the involvement of an EGFR/TGF alpha autocrine/paracrine pathway in the in vitro growth of both cell lines. Analysis of mice xenotransplanted s.c. with A431 cells and treated with MINT5 revealed a block in A431 tumor take in 6 of 10 animals when intact MAb was administered from day 0 to day 11. On a molar basis, F(ab')2 at the same dose was ineffective, although at a 7-fold higher dose F(ab')2 reduced s.c. tumor growth by 80%. At the same dose, intact MINT5 MAb reduced s.c. growth of the EGFR-negative MeWo cell line by 5%. Survival of mice bearing IGROVI i.p. xenotransplants and treated locally with either form of MAb was significantly prolonged even when treatment was initiated on day 3. Corrected doses of intact and F(ab')2 fragment, which accounted for the difference in serum half-lives of the MAb forms, resulted in similar survival rates in the tumor-bearing mice. These pre-clinical results suggest that MINT5 MAb might be safely used for systemic therapy of EGFR-over-expressing tumors. Loco-regional therapy might be contemplated in the case of tumors with moderate/low EGFR expression.

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Section: Discussioncontrasting

confidence: 85%

Anti‐tumor efficacy of an anti‐epidermal‐growth‐factor‐ receptor monoclonal antibody and its F(ab′)₂ fragment against high‐ and low‐egfr‐expressing carcinomas in nude mice

Tosi

Valota

Negri

et al. 1995

Intl Journal of Cancer

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“…Therefore, drugs such as anti-EGFR monoclonal antibodies and the specific inhibitor of the EGFR tyrosine kinase, which have been shown to inhibit the growth of cancer cells 'in vitro ' and 'in vivo' (Kurachi et al, 1991;Moreshige et al, 1991;Fry et al, 1994;Schnurch et al, 1994), may find use in ovarian cancer therapy.…”

Section: Resultsmentioning

confidence: 99%

Epidermal growth factor, oestrogen and progesterone receptor expression in primary ovarian cancer: correlation with clinical outcome and response to chemotherapy

Scambia

Benedetti‐Panici²,

Ferrandina³

et al. 1995

Br J Cancer

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Summary The expression of epidermal growth factor receptor (EGFR), oestrogen receptor (ER) and progesterone receptor (PR) was assayed by a radioreceptor method in 117 primary ovarian cancers. EGFR was not significantly related to any of the clinicopathological parameters examined. In patients with stage II-IV disease who underwent second-look surgery after primary chemotherapy, a significant correlation between high EGFR levels and poor response to chemotherapy was demonstrated (P = 0.031). Moreover, post-operative residual tumour showed an independent role in predicting chemotherapy response (P = 0.0007) and EGFR status showed a borderline significance (P = 0.052) in the multivariate analysis. No correlation between steroid hormone receptors and clinicopathological parameters was observed. Whereas a significant relationship was shown between EGFR positivity and a shorter overall survival (OS) (P = 0.0022) and progression-free survival (PFS) (P = Neal et al., 1991;Maurizi et al., 1992; Scambia et al., 1994). Moreover, in breast cancer EGFR expression seems to be a feature of hormone-independent aggressive clinical behaviour (Klijn et al., 1992). Our previous study The membrane fraction and cytosol were prepared as described elsewhere . Briefly, tumour specimens were finely minced and homogenised in five volumes of ice-cold buffer consisting of 25 mM Tris, 1.5 mM EDTA, 5 mM sodium azide, 20% glycerol (TENG) plus 0.1 % monothioglycerol, by applying several intermittent bursts of an Ultra-Turrax homogeniser. The crude homogenate was centrifuged at 7000 g for 20 min at 0°C in order to separate nuclear fraction from the cytosol fraction. The supernatants were then centrifuged at 105 000 g for 75 min at 0°C, obtaining the membrane pellet and the cytosolic fraction.

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“…Die Bindung von Antikörpern alleine wirkt nicht hinreichend antineoplastisch. Sie führt jedoch in der Regel zu einer "antibody dependend cellular cytotoxicity" (ADCC) im Tumormileu und kann im Tierversuch erhebliche Tumorverkleinerungen bewirken [54].…”

Section: Monoklonale Antikörperunclassified

Immunologische und innovative Therapieformen beim Ovarialkarzinom

Schnürch

1997

Gynäkologe

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Growth inhibition of xenotransplanted human carcinomas by a monoclonal antibody directed against the epidermal growth factor receptor

Cited by 21 publications

References 13 publications

Anti‐tumor efficacy of an anti‐epidermal‐growth‐factor‐ receptor monoclonal antibody and its F(ab′)₂ fragment against high‐ and low‐egfr‐expressing carcinomas in nude mice

Anti‐tumor efficacy of an anti‐epidermal‐growth‐factor‐ receptor monoclonal antibody and its F(ab′)₂ fragment against high‐ and low‐egfr‐expressing carcinomas in nude mice

Epidermal growth factor, oestrogen and progesterone receptor expression in primary ovarian cancer: correlation with clinical outcome and response to chemotherapy

Immunologische und innovative Therapieformen beim Ovarialkarzinom

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Growth inhibition of xenotransplanted human carcinomas by a monoclonal antibody directed against the epidermal growth factor receptor

Cited by 21 publications

References 13 publications

Anti‐tumor efficacy of an anti‐epidermal‐growth‐factor‐ receptor monoclonal antibody and its F(ab′)2 fragment against high‐ and low‐egfr‐expressing carcinomas in nude mice

Anti‐tumor efficacy of an anti‐epidermal‐growth‐factor‐ receptor monoclonal antibody and its F(ab′)2 fragment against high‐ and low‐egfr‐expressing carcinomas in nude mice

Epidermal growth factor, oestrogen and progesterone receptor expression in primary ovarian cancer: correlation with clinical outcome and response to chemotherapy

Immunologische und innovative Therapieformen beim Ovarialkarzinom

Contact Info

Product

Resources

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Anti‐tumor efficacy of an anti‐epidermal‐growth‐factor‐ receptor monoclonal antibody and its F(ab′)₂ fragment against high‐ and low‐egfr‐expressing carcinomas in nude mice

Anti‐tumor efficacy of an anti‐epidermal‐growth‐factor‐ receptor monoclonal antibody and its F(ab′)₂ fragment against high‐ and low‐egfr‐expressing carcinomas in nude mice