Expression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor

<p>Abstract</p> <p>Background</p> <p>Cervical cancer continues to be an important worldwide health problem for women. Up to 35% of patients who are diagnosed with and appropriately treated for cervical cancer will recur and treatment results are poor for recurrent disease. Given these sobering statistics, development of novel therapies for cervical cancer remains a high priority. We evaluated the expression of Tissue Factor (TF) in cervical cancer and the potential of hI-con1, an antibody-like-molecule targeted against TF, as a novel form of immunotherapy against multiple primary cervical carcinoma cell lines with squamous- and adenocarcinoma histology.</p> <p>Methods</p> <p>Because TF is a transmembrane receptor for coagulation factor VII/VIIa (fVII), in this study we evaluated the <it>in vitro </it>expression of TF in cervical carcinoma cell lines by immunohistochemistry (IHC), real time-PCR (qRT-PCR) and flow cytometry. Sensitivity to hI-con1-dependent cell-mediated-cytotoxicity (IDCC) was evaluated in 5-hrs-⁵¹chromium-release-assays against cervical cancer cell lines <it>in vitro</it>.</p> <p>Results</p> <p>Cytoplasmic and/or membrane TF expression was observed in 8 out of 8 (100%) of the tumor tissues tested by IHC and in 100% (11 out of 11) of the cervical carcinoma cell lines tested by real-time-PCR and flow cytometry but not in normal cervical keratinocytes (<it>p </it>= 0.0023 qRT-PCR; <it>p </it>= 0.0042 flow cytometry). All primary cervical cancer cell lines tested overexpressing TF, regardless of their histology, were highly sensitive to IDCC (mean killing ± SD, 56.2% ± 15.9%, range, 32.4%-76.9%, <it>p </it>< 0.001), while negligible cytotoxicity was seen in the absence of hI-con1 or in the presence of rituximab-control-antibody. Low doses of interleukin-2 further increased the cytotoxic effect induced by hI-con1 (<it>p </it>= 0.025) while human serum did not significantly decrease IDCC against cervical cancer cell lines (<it>p </it>= 0.597).</p> <p>Conclusions</p> <p>TF is highly expressed in squamous and adenocarcinoma of the uterine cervix. hI-con1 induces strong cytotoxicity against primary cervical cancer cell lines overexpressing TF and may represent a novel therapeutic agent for the treatment of cervical cancer refractory to standard treatment modalities.</p

Semi-synthetic minimal cells as a tool for biochemical ICT.

Biological systems evolved with the ability to communicate with their biotic surroundings through chemical signalling. Production, perception and decoding of the information carried by signal molecules allow individuals of a community to interact, cooperate, and coordinate their activities, establishing complex social behaviours. In this paper we speculate about the opportunity to use semi-synthetic minimal cells (SSMCs) as artificial entities able to communicate, by processing biochemical information, with natural systems. SSMCs are liposome-based cell-like molecular assemblies designed for displaying minimal cellular functions, like gene transcription and translation. The technological advancements in the last few years led to successful production of functional proteins in SSMCs raises the possibility to generate semi-synthetic cell-like. systems expressing the biochemical apparatus for signal molecules production, perception and decoding. The variety of chemical "languages" evolutionary selected by bacteria to communicate provides a broad spectrum of biochemical opportunities exploitable to reach this goal in the near future. More in general, the consequences arising from the construction of synthetic systems capable of communicating with natural living organisms would greatly impact the applications of synthetic biology and biochemical-based information and communication technologies (ICTs) in medical sciences, for example for smart programmable and drug-producing systems

Aggregation-Induced Electrochemiluminescence of Platinum(II) Complexes

We report the electrochemiluminescence properties of square-planar Pt­(II) complexes that result from the formation of supramolecular nanostructures. We define this new phenomenon as aggregation-induced electrochemiluminescence (AIECL). In this system, self-assembly changes the HOMO and LUMO energies, making their population accessible via ECL pathways and leading to the generation of the luminescent excited state. Significantly, the emission from the self-assembled system is the first example of electrochemiluminescence (ECL) of Pt­(II) complexes in aqueous solution having higher efficiency than the standard, Ru­(bpy)₃²⁺.The finding can lead to a new generation of bright emitters that can be used as ECL labels

Towards the engineering of chemical communication between semi-synthetic and natural cells

The recent advancements in semi-synthetic minimal cell (SSMC) technology paves the way to several interesting scenarios that span from basic scientific advancements to applications in biotechnology. In this short chapter we discuss the relevance of establishing chemical communication between synthetic and natural cells as an important conceptual question, and then discuss it as a new bio/chemical-information & communication technology. At this aim, the state-of-the-art of SSMCs technology is shortly reviewed, and a possible experimental ap-proach based on bacteria quorum sensing mechanisms is proposed and discussed

Cardiac Troponin I: Ultrasensitive Detection Using Faradaic Electrochemical Impedance

An electrochemical biosensor for the detection of cardiac troponin I, cTnI, an important cardiac biomarker, is described. A combination of a novel monoclonal antibody, mAb20B3, and a novel Ir(III)-based metal complex was used for detection using faradaic electrochemical impedance spectroscopy. A limit of detection of 10 ag/mL was achieved, which is significantly lower than established assays. The ability to detect these ultralow concentrations enables rapid and early stage detection of cardiac events and opens up the possibility of developing a point-of-care device