Rabbit Anti-Human CD8 Monoclonal Antibody, clone CQ7152

The use of biomarkers is integral to the routine management of cancer patients, including diagnosis of disease, clinical staging and response to therapeutic intervention. Advanced imaging metrics with computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) are used to assess response during new drug development and in cancer research for predictive metrics of response. Key components and challenges to identifying an appropriate imaging biomarker are selection of integral vs integrated biomarkers, choosing an appropriate endpoint and modality, and standardization of the imaging biomarkers for cooperative and multicenter trials. Imaging biomarkers lean on the original proposed quantified metrics derived from imaging such as tumor size or longest dimension, with the most commonly implemented metrics in clinical trials coming from the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and then adapted versions such as immune-RECIST (iRECIST) and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) for immunotherapy response and PET imaging, respectively. There have been many widely adopted biomarkers in clinical trials derived from MRI including metrics that describe cellularity and vascularity from diffusion-weighted (DW)-MRI apparent diffusion coefficient (ADC) and Dynamic Susceptibility Contrast (DSC) or dynamic contrast enhanced (DCE)-MRI (K-trans, relative cerebral blood volume (rCBV)), respectively. Furthermore, Fluorodexoyglucose (FDG), fluorothymidine (FLT), and fluoromisonidazole (FMISO)-PET imaging, which describe molecular markers of glucose metabolism, proliferation and hypoxia have been implemented into various cancer types to assess therapeutic response to a wide variety of targeted- and chemotherapies. Recently, there have been many functional and molecular novel imaging biomarkers that are being developed that are rapidly being integrated into clinical trials (with anticipation of being implemented into clinical workflow in the future), such as artificial intelligence (AI) and machine learning computational strategies, antibody and peptide specific molecular imaging, and advanced diffusion MRI. These include prostate-specific membrane antigen (PSMA) and trastuzumab-PET, vascular tumor burden extracted from contrast-enhanced CT, diffusion kurtosis imaging, and CD8 or Granzyme B PET imaging. Further excitement surrounds theranostic procedures such as the combination of Ga-68/In-111- and Lu-177-DOTATATE to use integral biomarkers to direct care and personalize therapy. However, there are many challenges in the implementation of imaging biomarkers that remains, including understand the accuracy, repeatability and reproducibility of both acquisition and analysis of these imaging biomarkers. Despite the challenges associated with the biological and technical validation of novel imaging biomarkers, a distinct roadmap has been created that is being implemented into many clinical trials to advance the development and implementation to create specific and sensitive novel imaging biomarkers of therapeutic response to continue to transform medical oncology. (C) 2020 Elsevier Inc. All rights reserved.

Interleukin-15 (IL-15) is a member of the IL-2 family of cytokines, which use receptor complexes containing the common gamma (gamma(c)) chain for signaling. IL-15 plays important roles in innate and adaptative immune responses and is implicated in the pathogenesis of several immune diseases. The IL-15 receptor consists of 3 subunits namely, the ligand-binding IL-15R alpha chain, the beta chain (also used by IL-2) and the gamma(c) chain. IL-15 uses a unique signaling pathway whereby IL-15 associates with IL-15R alpha during biosynthesis, and this complex is 'trans-presented' to responder cells that expresses the IL-2/15R beta gamma(c) receptor complex. IL-15 is subject to post-transcriptional and post-translational regulation, and evidence also suggests that IL-15 cis-signaling can occur under certain conditions. IL-15 has been implicated in the pathology of various autoimmune diseases such as rheumatoid arthritis, autoimmune diabetes, inflammatory bowel disease, coeliac disease and psoriasis. Studies with pre-clinical models have shown the beneficial effects of targeting IL-15 signaling in autoimmunity. Unlike therapies targeting other cytokines, anti-IL-15 therapies have not yet been successful in humans. We discuss the complexities of IL-15 signaling in autoimmunity and explore potential immunotherapeutic approaches to target the IL-15 signaling pathway.