Effect of tumour necrosis factor and lipid A on functional and structural vascular volume in solid murine tumours

Weil, Peter A.; Bouma, Gerrit J.; Pijl, A. van der; Weitenberg, E. S.; Lam, Antonio Wong; Bloksma, N.

doi:10.1038/bjc.1990.366

Cited by 12 publications

(1 citation statement)

References 25 publications

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“…van de Wiel et al (1989) suggested that the broad interference of tumour blood supply was the major cause of necrosis of Meth A sarcomas in mice, since TNF did not affect the Meth A cells in vitro. TNF has been shown to increase vascular permeability in vivo immediately after injection (Kallinowski et al, 1989), and to affect the functional and structural vascular volume in solid murine tumours (van de Wiel et al, 1990). Since poor vasculature is one of the factors limiting antibody uptake in tumours (Jain, 1991), if tumour vascular permeability could be increased by the administration of TNF, this would facilitate antibody access to tumour cell antigens.…”

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confidence: 99%

Effect of tumour necrosis factor on the uptake of specific and control monoclonal antibodies in a human tumour xenograft model

Rowlinson-Busza

Maraveyas²,

Epenetos³

1995

Br J Cancer

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Summary The investigations reported in this paper aim to exploit tumour necrosis factor (TNF)-induced vascular changes in an attempt to increase the tumour uptake of specific monoclonal antibody. The vascular permeability to monoclonal antibody of a human tumour xenograft increased 2.6-fold by 1 h post injection of 2.5 x 103 U of TNF, although this effect was lost by 3 h. The normal tissues also demonstrated increased vascular permeability to IgG, but to a lesser exent. Liver permeability increased 1.5-fold at I h but returned to the control value by 6 h. Lung permeability increased 1.4-fold at 1 h post injection and returned to normal by 3 h. Muscle values were not significantly increased compared with controls. The blood activity was cleared more quickly in the TNF-treated mice (ti = 101 h, compared with 121 h in control mice). This was probably due to the increased vascular permeability in normal organs of treated mice. At I day and 3 days post injection, the tumour uptake of the specific, but not the control, antibody was significantly increased by 25% and 29% respectively. This resulted in an increase in the area under the tumour activity curve, and therefore tumour radiation dose, of 25% in treated compared with control mice. In addition, a consequence of the faster blood clearance of the isotope in the TNF-treated mice was a reduction in the area under the blood activity curve of 12%, thereby reducing systemic toxicity. The increase in vascular permeability to IgG following TNF injection resulted in both specific and control antibodies having improved access to the tumour antigens, and a transient increase in uptake was observed. Only in the case of the specific antibody was the increase maintained, since this antibody binds to the available antigenic sites, whereas the control antibody was cleared from the tumour without binding. No evidence of tumour necrosis was observed at the TNF doses given, nor was there any toxicity to the mice.

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confidence: 99%

Effect of tumour necrosis factor on the uptake of specific and control monoclonal antibodies in a human tumour xenograft model

Rowlinson-Busza

Maraveyas²,

Epenetos³

1995

Br J Cancer

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Binding of some metastatic tumor cell lines to fibrous elastin and elastin peptides

Svitkina

Parsons

1993

Intl Journal of Cancer

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Recent suggestions that tumor-cell targeting of elastin-rich tissues (e.g., lung) correlates with the presence of surface elastin receptors have been investigated. Receptors for insoluble (fibrous) elastin and for soluble elastin peptides have been implemented in these correlations. A rapid assay for binding of insoluble elastin has been devised. Two of the cell lines tested (M27 and MAT-LyLu), which metastasize to the lung, strongly bound fibrous elastin whereas a third (B16-F10) did not. None of 4 metastatic cell lines that do not target the lung (A549, 3LL, TA3, TA3-iso2) bound fibrous elastin. The ability of cell lines to interact with soluble elastin was tested by cell attachment to high-molecular-weight soluble elastin peptides adsorbed on a plastic surface. Three of 7 tested cell lines, B16-F10, M27 and TA3, attached to a soluble elastin coating. In contrast to the rapid binding of insoluble elastin particles, the cell interaction with immobilized soluble elastin peptides was delayed, suggesting that induction of receptors for soluble elastin and/or modification of the elastin coat was occurring. Thus, all 3 tested cell lines where metastases target the lung, namely, MAT-LyLu, B16-F10 and M-27, show soluble- or insoluble-elastin interactions, whereas, of 4 cell lines not targeting lungs, only one, TA3, reacts with soluble elastin.

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

Folli

Pèlegrin

Chalandon

et al. 1993

Intl Journal of Cancer

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Marked differences in the tumor uptake of a 125I-labeled monoclonal antibody (MAb) directed against carcinoembryonic antigen (CEA) were observed in 4 serially transplanted human colorectal carcinomas in nude mice. A comparative study showed that elevated values of measurable tumor vascular parameters, such as permeability, blood flow and blood volume, correlated better with high MAb tumor uptake than the concentration of target antigen in the tumor. In an attempt to modify the vascular parameters and to determine if this could increase antibody uptake by the tumor, rhTNF alpha (TNF) was injected i.t. or i.v. and antibody localization experiments were performed immediately thereafter. Results showed that the permeability of the tumor vessels increased 8 to 10 fold 1 hr after i.t. injection of TNF as compared to control tumors injected with saline. Tumor uptake of 125I-labeled anti-CEA MAb, was 3 times higher 2 hr after i.v. injection and still 27% higher 22 hr later, as compared to results from controls. Intravenous injection of TNF simultaneously with the 125I-labeled anti-CEA MAb also resulted in a 2-fold increase in tumor uptake 4 hr after injection, but the increase was no longer significant 24 hr after injection. Interestingly after i.v. injection of TNF, the MAb concentration in the blood and other normal tissues, such as liver, kidneys, lungs and heart was decreased, resulting in significantly higher ratios of tumor to normal tissue. Taken together the results demonstrate that injection of TNF can increase tumor vascular permeability and improve radio-antibody uptake. This raises the possibility of increasing the radiation dose delivered by antibody to the tumor in the course of radioimmunotherapy.

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Effect of tumour necrosis factor and lipid A on functional and structural vascular volume in solid murine tumours

Cited by 12 publications

References 25 publications

Effect of tumour necrosis factor on the uptake of specific and control monoclonal antibodies in a human tumour xenograft model

Effect of tumour necrosis factor on the uptake of specific and control monoclonal antibodies in a human tumour xenograft model

Binding of some metastatic tumor cell lines to fibrous elastin and elastin peptides

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

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