Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with an immune suppressive phenotype. They represent a critical component of the immune suppressive niche described in cancer, where they support immune escape and tumor progression through direct effects on both the innate and adaptive immune responses, largely by contributing to maintenance of a high oxidative stress environment. The number of MDSCs positively correlates with protumoral activity, and often diminishes the effectiveness of immunotherapies, which is particularly problematic with the emergence of personalized medicine. Approaches targeting MDSCs showed promising results in preclinical studies and are under active investigation in clinical trials in combination with various immune checkpoint inhibitors. In this review, we discuss MDSC targets and therapeutic approaches targeting MDSC that have the aim of enhancing the existing tumor therapies.
BackgroundThere is now a renewed interest in cancer vaccines. Patients responding to immune checkpoint blockade usually bear tumors that are heavily infiltrated by T cells and express a high load of neoantigens, indicating that the immune system is involved in the therapeutic effect of these agents; this finding strongly supports the use of cancer vaccine strategies. Lymphoplasmacytic lymphoma (LPL) is a low grade, incurable disease featuring an abnormal proliferation of Immunoglobulin (Ig)-producing malignant cells. Asymptomatic patients are currently managed by a “watchful waiting” approach, as available therapies provide no survival advantage if started before symptoms develop. Idiotypic determinants of a lymphoma surface Ig, formed by the interaction of the variable regions of heavy and light chains, can be used as a tumor-specific marker and effective vaccination using idiotypes was demonstrated in a positive controlled phase III trial.MethodsThese variable region genes can be cloned and used as a DNA vaccine, a delivery system holding tremendous potential for streamlining vaccine production. To increase vaccination potency, we are targeting antigen-presenting cells (APCs) by fusing the antigen with a sequence encoding a chemokine (MIP-3α), which binds an endocytic surface receptor on APCs. Asymptomatic phase LPL is an excellent model to test our vaccine since patients have not received chemotherapeutics that interfere with innate immune function and have low tumor burden. We are evaluating the safety of this next-generation DNA vaccine in a first-in-human clinical trial currently enrolling asymptomatic LPL patients. To elucidate the mode of action of this vaccine, we will assess its ability to generate tumor-specific immune responses and examine changes in the immune profile of both the peripheral blood and bone marrow.DiscussionThis vaccine could shift the current paradigm of clinical management for patients with asymptomatic LPL and inform development of other personalized approaches.Trial registrationClinicalTrials.gov identifier NCT01209871; registered on September 24, 2010.
L-3 Communications CyTerra Corporation has developed a high throughput universal explosive detection system (PassPort) to automatically screen the passengers in airports without requiring them to remove their shoes. The technical approach is based on the patented energetic material detection (EMD) technology. By analyzing the results of sample heating with an infrared camera, one can distinguish the deflagration or decomposition of an energetic material from other clutters such as flammables and general background substances. This becomes the basis of a universal explosive detection system that does not require a library and is capable of detecting trace levels of explosives with a low false alarm rate. The PassPort is a simple turnstile type device and integrates a non-intrusive aerodynamic sampling scheme that has been shown capable of detecting trace levels of explosives on shoes. A detailed description of the detection theory and the automated sampling techniques, as well as the field test results, will be presented.
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