Tumor‐necrosis factor can enhance radio‐antibody uptake in human colon carcinoma xenografts by increasing vascular permeability

Folli, Silvio; Pèlegrin, André; Chalandon, Yves; Yao, Xiaofei; Buchegger, Franz; Líénard, Danielle; Lejeune, Ferdy J.; Mach, Jean‐Pierre

doi:10.1002/ijc.2910530521

Cited by 98 publications

(65 citation statements)

References 19 publications

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“…A direct correlation between the accumulation of MAbs in melanoma xenografts and the density of a cell surface melanoma-associated glycoprotein has been reported by Shockley et al (1992b). Similarly, a positive relationship between CEA content in tumor tissue and uptake of anti-CEA MAbs has been observed in vivo (Vogel et al, 1996), although in other studies on anti-CEA MAbs no clear correlation was observed (Blumenthal et al, 1992;Folli et al, 1993).…”

Section: Discussionmentioning

confidence: 72%

Determination of tumor-related factors of influence on the uptake of the monoclonal antibody 323/A3 in experimental human ovarian cancer

et al. 1997

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The epithelial glycoprotein 40 (EGP40) is an important target in the clinic for radioimmunolocalization and monoclonal antibody (MAb)-mediated therapy of cancer. We determined which tumor-related factors (including antigen distribution and density, vascularization and perfusion) were involved in the uptake of the anti-EGP40 MAb 323/A3 in 4 different human ovarian cancer xenografts grown s.c. in nude mice. The reactivity pattern of 323/A3 in all xenografts in vitro was similar and showed a strong and homogeneous distribution of the EGP40 antigen. FMa xenografts, however, showed the highest uptake of 323/A3 in vivo, which was 5.5-, 6.2-and 10.0-fold higher than that in OVCAR-3, Ov.Pe and Ov.Sh xenografts, respectively. FMa xenografts contained 2.1-to 3.5-fold more antigen per gram protein when compared with the antigen content of the other xenografts. FMa and Ov.Sh xenografts demonstrated a better vascularization pattern, whereas Ov.Pe and OVCAR-3 xenografts were moderately to poorly vascularized. FMa xenografts were also better perfused, as was shown by a 1.6-to 1.8-fold higher uptake of the 99m Tc-labeled blood flow marker hexamethylpropyleneamine oxime (HMPAO). The tumor uptake of the non-specific MAb E48 was 2.2-to 11.2-fold lower when compared with that of 323/A3, but the sequence of uptake was similar (FMa G OVCAR-3 5 Ov.Pe G Ov.Sh), indicating the lowest extravasation of MAbs in Ov.Sh xenograft tissue. Since both the antigen content and the perfusion appeared to be important factors of influence on the tumor uptake of 323/A3, attempts were made to manipulate these determinants to improve the tumor uptake. Neither g-interferon nor 5-fluorouracil were able to increase EGP40 expression in human ovarian cancer cells in vitro. Treatment of tumor-bearing mice with the calcium-antagonist flunarizine did not result in an improved perfusion, although a slight increase in the initial tumor uptake of 323/A3 was observed in Ov.Sh-bearing mice. Our results illustrate the relative contribution of various tumorrelated factors that determine the usefulness of a MAb for imaging and therapy of cancer. Int.

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Section: Discussionmentioning

confidence: 72%

Determination of tumor-related factors of influence on the uptake of the monoclonal antibody 323/A3 in experimental human ovarian cancer

et al. 1997

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“…Because human colon carcinoma s.c. grafted into nude mice give no detectable circulating CEA (Folli et al, 1993), we used a CEA-negative clone of the colon carcinoma cell line CO115 transfected with truncated CEA-cDNA lacking the 78 base pairs at the 3′ region encoding the 26-amino acid hydrophobic domain. This transfected cell line, CO115-2C2, was shown to actively secrete CEA into the culture (Terskikh et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Involvement of circulating CEA in liver metastases from colorectal cancers re-examined in a new experimental model

Leconte¹,

Garambois²,

Ychou³

et al. 1999

Br J Cancer

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Summary Both experimental and clinical data show evidence of a correlation between elevated blood levels of carcinoembryonic antigen (CEA) and the development of liver metastases from colorectal carcinomas. However, a cause-effect relationship between these two observations has not been demonstrated. For this reason, we developed a new experimental model to evaluate the possible role of circulating CEA in the facilitation of liver metastases. A CEA-negative subclone from the human colon carcinoma cell line CO115 was transfected either with CEAcDNA truncated at its 3′ end by the deletion of 78 base pairs leading to the synthesis of a secreted form of CEA or with a full-length CEA-cDNA leading to the synthesis of the entire CEA molecule linked to the cell surface by a GPI anchor. Transfectants were selected either for their high CEA secretion (clone CO115-2C2 secreting up to 13 µg CEA per 10 6 cells within 72 h) or for their high CEA membrane expression (clone CO115-5F12 expressing up to 1 × 10 6 CEA molecules per cell). When grafted subcutaneously, CO115-2C2 cells gave rise to circulating CEA levels that were directly related to the tumour volume (from 100 to 1000 ng ml -1 for tumours ranging from 100 to 1000 mm 3 ), whereas no circulating CEA was detectable in CO115 and CO115-5F12 tumour-bearing mice. Three series of nude mice bearing a subcutaneous xenograft from either clone CO115-2C2 or the CO115-5F12 transfectant, or an untransfected CO115 xenograft, were further challenged for induction of experimental liver metastases by intrasplenic injection of three different CEA-expressing human colorectal carcinoma cell lines (LoVo, LS174T or CO112). The number and size of the liver metastases were shown to be independent of the circulating CEA levels induced by the subcutaneous CEA secreting clone (CO115-2C2), but they were directly related to the metastatic properties of the intrasplenically injected tumour cells.

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“…Thus, the previously demonstrated increase in antibody uptake 1-4 h after i.v. TNF-a injection (Folli et al, 1993;RowlinsonBusza et al, 1995) might still be explained by an increase in vascular permeability surface area product and/or convection across the microvascular wall.…”

Section: Discussionmentioning

confidence: 99%

Reduction of interstitial fluid pressure after TNF-alpha treatment of three human melanoma xenografts

Kristensen

Nozue²,

Boucher³

et al. 1996

Br J Cancer

107

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Summary Tumour necrosis factor-a (TNF-a) reduced the interstitial fluid pressure (IFP) to 54-64% (P<0.05) and the mean arterial blood pressure (MABP) to 70% (P<0.01) of control values after 5 h in three human melanoma tumour lines transplanted to nude mice.Keywords: tumour necrosis factor-a; interstitial fluid pressure; melanoma xenograft; blood pressure Tumour necrosis factor-a (TNF-a) or cachectin has been proposed as a potential anti-cancer agent for clinical application owing to a remarkable activity of this biological response modifier against several types of murine neoplasms (Asher et al., 1987). Furthermore, TNF-a seems to play an important vasodilatory role in host response to septic insults (Tracey et al., 1987), potentially mediated by the release of nitric oxide (NO) from endothelial cells or macrophages (Baudry and Vicaut, 1993;Kilbourn et al., 1990). The combination of TNF-a, melphalan and interferon-y in regional perfusion of human extremity sarcomas and melanomas has resulted in impressive response rates (Vaglini et al., 1994;Lienard et al., 1992), presumably owing to a combined early effect on tumour vasculature and a possible immune enhancement effect of TNF-a (Fraker and Alexander, 1993). A relationship between production of vascular endothelial growth factor (VEGF) and TNF-a cytotoxicity has been demonstrated in vivo, supporting the hypothesis of a vascular effect of TNF-a on tumour tissue (Amikura et al., 1995). Several studies have suggested that increased delivery of macromolecules (e.g. protein-bound chemotherapeutic agents, antibodies and DNA) can be achieved by lowering the interstitial fluid pressure (IFP) (Boucher and Jain, 1992;Boucher et al., 1991;Kristjansen et al., 1993;Zlotecki et al., 1993Zlotecki et al., , 1995 Mean arterial blood pressure Cannulation of the left carotid artery was performed after a longitudinal skin incision above the trachea. After removal of the submandibular gland, the paratracheal muscles were split and the left carotid artery was isolated. The cranial end of the artery was ligated with a 6-0 silk suture and another suture was tied loosely around the central part of the artery. A metal clamp was positioned caudally to stop the blood flow during the cannulation. A polyethylene catheter (PE-10; Becton-Dickinson, Sparks, MD, USA) filled with heparinised saline was inserted through a hole cut proximally to the cranial ligature, and the other suture was tied tightly around the tubing and artery. The clamp was removed and the end of the tubing was connected to a pressure transducer as described previously (Zlotecki et al., 1993

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Tumor‐necrosis factor can enhance radio‐antibody uptake in human colon carcinoma xenografts by increasing vascular permeability

Cited by 98 publications

References 19 publications

Determination of tumor-related factors of influence on the uptake of the monoclonal antibody 323/A3 in experimental human ovarian cancer

Determination of tumor-related factors of influence on the uptake of the monoclonal antibody 323/A3 in experimental human ovarian cancer

Involvement of circulating CEA in liver metastases from colorectal cancers re-examined in a new experimental model

Reduction of interstitial fluid pressure after TNF-alpha treatment of three human melanoma xenografts

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