In vivo Antitumor Mechanism of Natural Human Tumor Necrosis Factor Involving a T Cell‐mediated Immunological Route

Abstract

We have investigated the in vivo antitumor mechanism of natural human tumor necrosis factor (n‐TNF) isolated from a culture of human leukemic B cell line (BALL‐1), especially its action as an immunomodulator, and found that the in vivo antitumor effect of n‐TNF on Meth A sarcoma implanted in BALB/c mice pretreated with monoclonal antibody against T cell‐specific surface antigen (Thy‐1) was significantly diminished. Furthermore, when BALB/c mice were treated with T cell subset‐specific monoclonal antibodies, anti‐L3T4 or anti‐Lyt‐2.2, the antitumor effect of n‐TNF on Meth A sarcoma was significantly reduced. Therefore, it was suggested that the in vivo antitumor mechanism of n‐TNF might involve a T cell‐mediated immunological route.

Colloidal gold nanoparticles: a novel nanoparticle platform for developing multifunctional tumor‐targeted drug delivery vectors

“…In effect, by localizing the delivery of TNF to solid tumors, Lienard and Lejuene harnessed the biology of TNF to induce at least one of the possible mechanisms by which the cytokine induces an anti-tumor response. For example, TNF has been shown to cause apoptosis directly in various tumor cell types Helson et al, 1975], to activate and drive immune-based anti-tumor responses [Asami et al, 1989], and to induce vascular leak in tumor blood vessels [Nawroth and Stern, 1986;Brett et al, 1989], leading to a destruction of the interstitial fluid pressure (IFP) gradient in solid tumors [Kristensen et al, 1996;Nedrebo et al, 1999]. Thus, the rational design of nanotherapeutics that simulate this surgical procedure may prove to be an effective strategy to developing new tumor-targeted therapies.…”

Isolierte Extremitätenperfusion mit TNFα und Zytostatika: eine Revolution in der Behandlung lokal fortgeschrittener Weichgewebssarkome der Extremitäten

“…Early reports revealed a dual effect: a small direct cytotoxic activity on, at least some, tumor cell lines mediated by the apoptotic pathway and an immune stimulatory activity [86][87][88]; and a vast selective disruption of the tumor-associated vessels, inducing hemorrhagic necrosis [89,90].…”

Anti-tumor action of tumor necrosis factor against Bomirski Ab melanoma in hamsters

“…As indicated in the literature, tumor regression is entirely dependent on T lymphocytes [ 4 , 22 , 50 ]. A suggested mechanism of this process is that TNF activates Th lymphocytes which in turn activate cytotoxic T lymphocytes (CTL) to destroy tumor cells [ 3 ]. Furthermore, some recent experiments on knockout mice have indicated TNF together with perforin and interferon γ as a critical triad of effector molecules in anti-tumor activity of CTL [ 57 ].…”