Evaluation of Risk Parameters in Bone Regeneration Using a Customized Titanium Mesh: Results of a Clinical Study.

PURPOSE: The aim of the study was an evaluation of risk factors for an innovative bone regeneration technique using a customized titanium mesh that was tested in a clinical setting. MATERIALS AND METHODS: This retrospective study included 65 patients with 70 grafting procedures of osseous defects of the jaws with a customized titanium mesh together with Advanced- and Injectable-Platelet-Rich Fibrin (A- and I-PRF), resorbable membranes, and bone grafting materials. Exposures of the meshes and grafting outcome were analyzed according to a novel classification as (a) punctual and (b) tooth width or complete exposure of the mesh (c). No exposure was stated as (d). RESULTS: In 37% of cases, exposures of the meshes occurred that were significantly associated with loss of grafted material (P < 0.001). Tobacco abuse (P = 0.032) and grafting procedures together with simultaneous sinus floor elevation techniques (P = 0.001) were found to be risk factors for success of the grafted material. Implant placement was not possible in 2 cases only. CONCLUSION: The results of this study verified the treatment of large defects with a customized titanium mesh as a useful protocol with a predictable outcome, even in cases of dehiscences.

Engineering of Anti-CD133 Trispecific Molecule Capable of Inducing NK Expansion and Driving Antibody-Dependent Cell-Mediated Cytotoxicity.

PURPOSE: The selective elimination of cancer stem cells (CSCs) in tumor patients is a crucial goal because CSCs cause drug refractory relapse. To improve the current conventional bispecific immune-engager platform, a 16133 bispecific natural killer (NK) cell engager (BiKE), consisting of scFvs binding FcγRIII (CD16) on NK cells and CD133 on carcinoma cells, was first synthesized and a modified interleukin (IL)-15 crosslinker capable of stimulating NK effector cells was introduced. MATERIALS AND METHODS: DNA shuffling and ligation techniques were used to assemble and synthesize the 1615133 trispecific NK cell engager (TriKE). The construct was tested for its specificity using flow cytometry, cytotoxic determinations using chromium release assays, and lytic degranulation. IL-15-mediated expansion was measured using flow-based proliferation assays. The level of interferon (IFN)-γ release was measured because of its importance in the anti-cancer response. RESULTS: 1615133 TriKE induced NK cell-mediated cytotoxicity and NK expansion far greater than that achieved with BiKE devoid of IL-15. The drug binding and induction of cytotoxic degranulation was CD133+ specific and the anti-cancer activity was improved by integrating the IL-15 cross linker. The NK cell-related cytokine release measured by IFN-γ detection was higher than that of BiKE. NK cytokine release studies showed that although the IFN-γ levels were elevated, they did not approach the levels achieved with IL-12/IL-18, indicating that release was not at the supraphysiologic level. CONCLUSION: 1615133 TriKE enhances the NK cell anti-cancer activity and provides a self-sustaining mechanism via IL-15 signaling. By improving the NK cell performance, the new TriKE represents a highly active drug against drug refractory relapse mediated by CSCs.

CD133, Selectively Targeting the Root of Cancer.

Cancer stem cells (CSC) are capable of promoting tumor initiation and self-renewal, two important hallmarks of carcinoma formation. This population comprises a small percentage of the tumor mass and is highly resistant to chemotherapy, causing the most difficult problem in the field of cancer research, drug refractory relapse. Many CSC markers have been reported. One of the most promising and perhaps least ubiquitous is CD133, a membrane-bound pentaspan glycoprotein that is frequently expressed on CSC. There is evidence that directly targeting CD133 with biological drugs might be the most effective way to eliminate CSC. We have investigated two entirely unrelated, but highly effective approaches for selectively targeting CD133. The first involves using a special anti-CD133 single chain variable fragment (scFv) to deliver a catalytic toxin. The second utilizes this same scFv to deliver components of the immune system. In this review, we discuss the development and current status of these CD133 associated biological agents. Together, they show exceptional promise by specific and efficient CSC elimination.