Imaging of T-cells and their responses during anti-cancer immunotherapy

Contains fulltext : 215809.pdf (publisher's version ) (Open Access)Immunotherapy has proven to be an effective approach in a growing number of cancers. Despite durable clinical responses achieved with antibodies targeting immune checkpoint molecules, many patients do not respond. The common denominator for immunotherapies that have successfully been introduced in the clinic is their potential to induce or enhance infiltration of cytotoxic T-cells into the tumour. However, in clinical research the molecules, cells and processes involved in effective responses during immunotherapy remain largely obscure. Therefore, in vivo imaging technologies that interrogate T-cell responses in patients represent a powerful tool to boost further development of immunotherapy. This review comprises a comprehensive analysis of the in vivo imaging technologies that allow the characterisation of T-cell responses induced by anti-cancer immunotherapy, with emphasis on technologies that are clinically available or have high translational potential. Throughout we discuss their respective strengths and weaknesses, providing arguments for selecting the optimal imaging options for future research and patient management

Strain-gradient-dependent stress-strain curve for normal-strength concrete

The stress-strain distribution of concrete in the compression zone of reinforced concrete (RC) flexural members is the most important parameter for assessing the ultimate flexural strength and ductility. Currently, the stress-strain curve of concrete developed in flexure is taken as the uni-axial compressive curve incorporating a scale-down factor k3, which is the ratio of the maximum concrete stress developed under flexure to the concrete cylinder strength. In current RC design codes, the ratio of the equivalent concrete stress to cylinder strength is taken as constant equal to 0.85 for normal-strength concrete but reduces as concrete strength increases. However, in a recent study carried out by the authors, it was found that the maximum concrete stress developed in the flexure increases significantly as the strain gradient (ratio of extreme concrete strain to neutral axis depth) increases, until reaching a maximum limit. Therefore, the value of k3 should not be taken as a constant for flexural RC members. In this study, the authors will adopt the results obtained in the previous experimental tests on concentrically, eccentrically and horizontally loaded RC columns to derive the stress-strain curve of concrete under different extents of strain gradient. The derived values of k3 are then correlated to the strain gradient using empirical equation. The applicability of the proposed equation is checked by comparing the flexural strengths of NSC beams and columns so calculated with those experimentally measured by different researchers, in which good agreement has been obtained

Evaluation of integrin αvβ₆ cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis.

Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvβ6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer’s safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin αvβ6