Tumor Necrosis Factor for the Treatment of Malignancies

Hieber, U.; Heim, Manfred

doi:10.1159/000227329

Cited by 74 publications

(38 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Systemic TNF therapy for cancer patients, especially at high doses, can cause toxicity (7,8). Although cancer patients may already have high TNF levels at the onset of therapy, perhaps accounting in part for the added toxicity, the fact remains the therapeutic window for TNF may be narrow.…”

Section: Discussionmentioning

confidence: 99%

“…TNFR1 is ubiquitously expressed on all T cell populations, the entire lymphoid system, and most other cells. This explains TNF's systemic toxicity when used at high doses in oncology treatment and in diseases with normal TNF basal levels (7,8). TNFR2, in contrast, is more restrictively expressed, found only on select subpopulations of T cells, endothelial cells, neurons, and other occasional cells (9).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Selective death of autoreactive T cells in human diabetes by TNF or TNF receptor 2 agonism

Ban

Zhang²,

Wang³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

117

123

View full text Add to dashboard Cite

Human autoimmune (AI) diseases are difficult to treat, because immunosuppressive drugs are nonspecific, produce high levels of adverse effects, and are not based on mechanistic understanding of disease. Destroying the rare autoreactive T lymphocytes causing AI diseases would improve treatment. In animal models, TNF selectively kills autoreactive T cells, thereby hampering disease onset or progression. Here, we seek to determine, in fresh human blood, whether TNF or agonists of TNF selectively kill autoreactive T cells, while sparing normal T cells. We isolated highly pure CD4 or CD8 T cells from patients with type 1 diabetes (n ‫؍‬ 675), other AI diseases, and healthy controls (n ‫؍‬ 512). Using two cell death assays, we found that a subpopulation of CD8, but not CD4, T cells in patients' blood was vulnerable to TNF or TNF agonist-induced death. One agonist for the TNFR2 receptor exhibited a doseresponse pattern of killing. In type 1 diabetes, the subpopulation of T cells susceptible to TNF or TNFR2 agonist-induced death was traced specifically to autoreactive T cells to insulin, a known autoantigen. Other activated and memory T cell populations were resistant to TNF-triggered death. This study shows that autoreactive T cells, although rare, can be selectively destroyed in isolated human blood. TNF and a TNFR2 agonist may offer highly targeted therapies, with the latter likely to be less systemically toxic.agonist antibodies ͉ autoimmunity ͉ apoptosis ͉ TNFR2 ͉ Crohn's

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Selective death of autoreactive T cells in human diabetes by TNF or TNF receptor 2 agonism

Ban

Zhang²,

Wang³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

117

123

View full text Add to dashboard Cite

show abstract

“…In particular, locoregional treatment with TNF-a appears to be promising (Hieber and Heim, 1994) and is currently under investigation Klaase et al, 1995). In this study we describe an assay to determine the level of TNF-a in liver and tumour tissue samples.…”

Section: Discussionmentioning

confidence: 99%

“…systemically administered TNF-a before life-threatening toxicities set in, while tumour regression in mice required a dose of approximately 400 ,ug kg-' (Blick et al, 1987;McIntosh et al, 1988;Hieber and Heim, 1994). The maximum-tolerated dose of TNF-x depends on the route of administration.…”

mentioning

confidence: 99%

Liver and tumour tissue concentrations of TNF-alpha in cancer patients treated with TNF-alpha and melphalan by isolated liver perfusion

Kuppen

Jonges²,

Velde³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary In this study we determined the level of tumour necrosis factor alpha (TNF-a) in liver and tumour tissue samples obtained from patients with colorectal metastases confined to the liver, who were treated with isolated liver perfusion with TNF-a and melphalan. We adapted a standard enzyme-linked immunosorbent assay kit for the quantification of TNF-a in serum to measure the amount of this cytokine in solid tissue. For this purpose, we developed a buffer that lysed the tissues without affecting the TNF-a present. The minimum detection level was about 2 pg of TNF-a per mg tissue. Using this technique, we found a significant increase in the TNF-a level after perfusion in the liver tissue of all evaluable patients, which may explain the transient liver toxicity we observed in all patients. In tumour tissue, a significant TNF-a increase was observed in one out of five patients. The level of TNF-a in all liver tissue samples and some of the tumours after treatment by isolated liver perfusion was much higher than the peak serum concentrations obtained after systemic administration of the maximum tolerated dose of TNF-a. Furthermore, we demonstrated that the level of TNF-a in the liver tissue samples was about seven to eight times higher than in tumour tissue. We concluded that regional liver treatment resulted in a relatively high local level of TNF-a, but also that this cytokine did not preferentially accumulate in tumour tissue.

show abstract

“…We have shown that in combination with hyperthermia or cryotherapy, TNF-a can induce significant tumor response (10,14). Unfortunately, systemic administration of TNF-a has dose-limiting toxicity (15,16). Therefore, there is a need for selective tumor delivery of TNF-a to minimize systemic toxicity.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of tumor thermal therapy using gold nanoparticle–assisted tumor necrosis factor-α delivery

Visaria

Griffin²,

Williams³

et al. 2006

Molecular Cancer Therapeutics

246

128

View full text Add to dashboard Cite

show abstract

Tumor Necrosis Factor for the Treatment of Malignancies

Cited by 74 publications

References 40 publications

Selective death of autoreactive T cells in human diabetes by TNF or TNF receptor 2 agonism

Selective death of autoreactive T cells in human diabetes by TNF or TNF receptor 2 agonism

Liver and tumour tissue concentrations of TNF-alpha in cancer patients treated with TNF-alpha and melphalan by isolated liver perfusion

Enhancement of tumor thermal therapy using gold nanoparticle–assisted tumor necrosis factor-α delivery

Contact Info

Product

Resources

About