Although biological therapy has shown promising clinical responses in many cancers including metastatic melanoma, only a subset of patients has shown marked regression of lesions. In most patients, systemic administration of biological therapies with cytokines is associated with severe toxicities. Schwager et al., in this issue of Journal of Investigative Dermatology, have examined the role of ...

We sought to enhance the selective toxicity of tumor necrosis factor (TNF ) to permit its systemic use in cancer therapy. Because ligand-targeted therapeutics have proven successful in improving the selective toxicity of drugs, we prepared a fusion protein (L19mTNF ) composed of mouse TNF and a high-affinity antibody fragment (L19 scFv) to the extradomain B (ED-B) domain of fibronectin, a marke...

L19-IL2 is a recombinant protein comprising the cytokine IL2 fused to the single-chain monoclonal antibody L19. In previous studies, intralesional injection with IL2 has shown efficacy for the locoregional treatment of cutaneous/subcutaneous metastases in patients with advanced melanoma. The objectives of this study were to investigate whether (i) intralesional delivery of a targeted form of IL...

We sought to enhance the selective toxicity of tumor necrosis factor (TNF ) to permit its systemic use in cancer therapy. Because ligand-targeted therapeutics have proven successful in improving the selective toxicity of drugs, we prepared a fusion protein (L19mTNF ) composed of mouse TNF and a high-affinity antibody fragment (L19 scFv) to the extradomain B (ED-B) domain of fibronectin, a marke...

Purpose: Radiotherapy modifies the tumor microenvironment and causes the release of tumor antigens, which can enhance the effect of immunotherapy. L19 targets the extra domain B (ED-B) of fibronectin, a marker for tumor neoangiogenesis, and can be used as immunocytokine when coupled to IL2. We hypothesize that radiotherapy in combination with L19-IL2 provides an enhanced antitumor effect, which...

We sought to enhance the selective toxicity of tumor necrosis factor alpha (TNFα) in order to permit its systemic use in cancer therapy. Since ligand-targeted therapeutics has proven successful in improving the selective toxicity of drugs, we prepared a fusion protein (L19mTNFα) composed of mouse TNFα and a high affinity antibody fragment (L19 scFv) to the ED-B domain of fibronectin, a marker o...

The S stars in the Galactic-center region are found to be on near-perfect Keplerian orbits around presumably a supermassive black hole, with periods of 15-50 yr. Since these stars reach a few percent of light speed at pericenter, various relativistic effects are expected and have been discussed in the literature. We argue that an elegant test of the Einstein equivalence principle should be poss...

Anti-angiogenic therapy of solid tumors has until now failed to produce the long lasting clinical benefits desired, possibly due to the complexity of the neoangiogenic process. Indeed, a prominent role is played by "vasculogenic" or "vascular" mimicry (VM), a phenomenon in which aggressive cancer cells form an alternative microvascular circulation, independently of endothelial cell angiogenesis...