Oncolytic Immunotherapy for Treatment of Cancer.

Immunotherapy entails the treatment of disease by modulation of the immune system. As detailed in the previous chapters, the different modes of achieving immune modulation are many, including the use of small/large molecules, cellular therapy, and radiation. Oncolytic viruses that can specifically attack, replicate within, and destroy tumors represent one of the most promising classes of agents for cancer immunotherapy (recently termed as oncolytic immunotherapy). The notion of oncolytic immunotherapy is considered as the way in which virus-induced tumor cell death (known as immunogenic cancer cell death (ICD)) allows the immune system to recognize tumor cells and provide long-lasting antitumor immunity. Both immune responses toward the virus and ICD together contribute toward successful antitumor efficacy. What is now becoming increasingly clear is that monotherapies, through any of the modalities detailed in this book, are neither sufficient in eradicating tumors nor in providing long-lasting antitumor immune responses and that combination therapies may deliver enhanced efficacy. After the rise of the genetic engineering era, it has been possible to engineer viruses to harbor combination-like characteristics to enhance their potency in cancer immunotherapy. This chapter provides a historical background on oncolytic virotherapy and its future application in cancer immunotherapy, especially as a combination therapy with other treatment modalities.

Molecular mechanisms underlying the regulation and functional plasticity of FOXP3(+) regulatory T cells.

CD4(+) CD25(+) regulatory T (Treg) cells engage in the maintenance of immunological self-tolerance and homeostasis by limiting aberrant or excessive inflammation. The transcription factor forkhead box P3 (FOXP3) is critical for the development and function of Treg cells. The differentiation of the Treg cell lineage is not terminal, as developmental and functional plasticity occur through the sensing of inflammatory signals in the periphery. Here, we review the recent progress in our understanding of the molecular mechanisms underlying the regulation and functional plasticity of CD4(+) CD25(+) FOXP3(+) Treg cells, through the perturbation of FOXP3 and its complex at a transcriptional, translational and post-translational level.

Single mode mid-infrared silver halide asymmetric flat waveguide obtained from crystal extrusion.

A flat waveguide for the middle infrared was made by co-extrusion of two silver halide crystals of different chemical compositions. The transmission of the waveguide and its modal behavior was studied using a Fourier Transform Spectrometer and a dedicated optical bench. Analyzing this spectrum, we were able to obtain the cut-off wavelength of the waveguide. We observed a single mode behavior for wavelengths longer than 8.83mum, in good agreement with the theoretically expected values. This novel procedure is ideal for tailoring the properties of the waveguide for specific applications, in particular the spectral range where it exhibits a single-mode behavior. It can thus be applied to achieve modal filtering for mid-IR astronomical interferometers (e.g. beam combiners, nullers, etc.).

Modal filtering for midinfrared nulling interferometry using single mode silver halide fibers.

We demonstrate the modal filtering properties of newly developed single mode silver halide fibers for use at midinfrared wavelengths, centered at 10.5 microm. The goal was to achieve a suppression of nonfundamental modes greater than a factor of 300 to enable the detection and characterization of Earthlike exoplanets with a space-based nulling interferometer. Fiber segments of 4.5 cm, 10.5 cm, 15 cm, and 20 cm lengths were tested. We find that the performance of the fiber was limited not by the modal filtering properties of the core but by the unsuppressed cladding modes present at the output of the fiber. In 10.5 cm and longer sections, this effect can be alleviated by properly aperturing the output. Exclusive of coupling losses, the fiber segments of 10.5-20 cm length can provide power suppression of undesirable components of the input field by a factor of 15,000 at least. The demonstrated performance thus far surpasses our requirements, such that even very short sections of fiber provide adequate modal filtering for exoplanet characterization.