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Radiopharmaceuticals for Diagnostics
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Jim Ballinger, Jacek Koziorowski
An alternative, non-colloidal agent was introduced in 2014. Tilmanocept (Lymphoseek) targets the CD206 mannose receptor on macrophages. Its soluble nature and moderate size allow it to leave the depot efficiently and migrate along lymphatic channels to lymph nodes. Its high affinity for the mannose receptor causes it to be tightly bound in first echelon nodes [32].
Order Picornavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
To enhance antigen uptake through mannose receptors, leading to improved immune responses, Al-Barwani et al. (2014) conjugated monomannoside and dimannoside to the insect cells-produced RHDV VLPs, providing approximately 270 mannose groups on the surface of each VLP. Such chimeric VLPs exhibited significantly enhanced binding and internalization by murine dendritic cells, macrophages, and B cells as well as human dendritic cells and macrophages. Moreover, fluorescently labeled VLPs conjugated to the mannoside or dimannoside were used to determine the effect of the VLP mannosylation on the VLP internalization and processing by key antigen-presenting cells. Kramer et al. (2019) conjugated mono- and dimannosides to the surface of the genetically constructed gp100-RHDV VLPs, which carried up to three copies of gp10025–33 epitope KVPRNQDWL, a melanoma-associated antigen, containing proteasome cleavable linkers to target the correct processing of the epitope. The mannosides were intended therefore to utilize a second pathway of internalization, mannose receptor mediated, to further augment antigens internalized by phagocytosis/macropinocytosis. It was demonstrated that the mannosylation of the chimeric RHDV VLPs translated into enhanced uptake of the VLPs and superior survival of mice in a melanoma tumor trial.
Platelet-Rich Plasma
Published in Rubina Alves, Ramon Grimalt, Techniques in the Evaluation and Management of Hair Diseases, 2021
Lu Yin, Katerina Svigos, Kristen Lo Sicco, Jerry Shapiro
Escobar et al. analyzed cell surface markers and cytokine production from human monocyte-derived macrophages after 24-hours of stimulation with allogeneic pure PRP (P-PRP) or supernatant of calcium-activated pure PRP (S-PRP). They found no difference in the expression of CD206, a mannose receptor associated with decreasing inflammation, which was increased in both groups. They also found increased CD163, a haptoglobin-hemoglobin scavenger receptor, and CD86, a pro-inflammatory marker, in the macrophages incubated in S-PRP compared to P-PRP. IL-10, an anti-inflammatory cytokine that promotes wound healing through activation of arginase 1 and ECM production [18], was secreted in greater amounts from cells incubated in P-PRP. This study was limited as it was allogeneic and the macrophages and plasma were not obtained from the same individuals. However, the results do suggest that calcium activation results in biochemical differences with respect to its effects on macrophages, which may translate to differences in clinical outcomes.
Old and novel prognostic biomarkers in primary biliary cholangitis
Published in Expert Opinion on Orphan Drugs, 2021
G Mulinacci, A Palermo, Pietro Invernizzi, Marco Carbone
Soluble CD163 (sCD163) marker is an endocytic receptor for haptoglobin-hemoglobin complex, found only on macrophages or monocytes. A correlation was demonstrated between its blood levels and the presence of liver fibrosis, portal hypertension, cirrhosis and increased in overall mortality in several hepatic disorders, including autoimmune hepatitis (AIH) [50–55]. Similar data were published with regards to the mannose receptor (MR), an endocytic receptor prevalently expressed in macrophages and dendritic cells and transported to the cell surface during inflammation. An increased concentration of the soluble form of this receptor, the soluble mannose receptor (sMR), was found in some liver diseases, such as Nonalcoholic Fatty Liver Disease (NAFLD) and Hepatitis B virus (HBV) infection [56]. We recently investigated the association between sCD163 and sMR levels with long-term prognosis in patients with PBC. Both markers were shown to increase in parallel with disease activity, i.e. ALP levels, and were correlated with hard outcomes (liver transplantation or liver-related death) in univariate analysis. However, only sCD163 confirmed its association after adjusting for confounders. Importantly, the addition of sCD163 to the UK-PBC risk score increased its prediction accuracy of poor outcome by 5,10 and 15 years [57].
Dual antitubercular drug loaded liposomes for macrophage targeting: development, characterisation, ex vivo and in vivo assessment
Published in Journal of Microencapsulation, 2021
Priya Shrivastava, Laxmikant Gautam, Rajeev Sharma, Devyani Dube, Sonal Vyas, Suresh P. Vyas
Macrophage expresses various receptors including fucose, mannose, galactose, and numerous others. The mannose receptor is known to have a critical role in the phagocytosis of Mycobacterium tuberculosis by human pneumocytes (alveolar macrophages) (Rajaram et al. 2017). Receptor-mediated phagocytosis especially operates in lung alveoli wherein the alveolar macrophages overexpress the mannose receptors (Irache et al. 2008, Vieira et al. 2017). Mannose receptor–ligand interaction also triggers the synthesis and secretion of anti-inflammatory cytokines including TNF-α, IL-1β, IL-6, and IL-23 and also reactive oxygen species (ROS) production (Chieppa et al. 2003, Zenaro et al. 2009). It appears to be beneficial to target bioactive(s) to the infected alveolar macrophages which are bio tropics that harbour pathogens. The macrophage targeting could improve the therapeutic efficacy and minimise the incidences of antitubercular bioactive(s) associated toxicity (Costa et al. 2018).
Glycoform-resolved pharmacokinetic studies in a rat model employing glycoengineered variants of a therapeutic monoclonal antibody
Published in mAbs, 2021
David Falck, Marco Thomann, Martin Lechmann, Carolien A. M. Koeleman, Sebastian Malik, Cordula Jany, Manfred Wuhrer, Dietmar Reusch
Previous publications have indicated the preferred clearance of high-mannose glycans.19,21,23 The total antibody measurements yielded only tendencies of increased clearance, reduced half-life, and reduced AUC for the M5 experiment. Low statistical power results partially from the necessary exclusion of two animals of the reference group. These animals showed a strongly increased clearance for unknown reasons (Figure S3). An initially suspected involvement of anti-drug antibodies could be excluded. Two of the six rats given the reference mAb showed anti-drug antibodies, but not the two rats with increased clearance (data not shown). In addition, the total PK measurement is a sum of the clearance of the heterogenic glycovariants and subtle differences in clearance values may not be detectable. Fortunately, the glycoform-resolved PK calculations allowed a paired intra-individual comparison. Consequently, we could reproduce the strongly increased clearance of high-mannose-type glycoforms. A 1.8 to 2.6-fold increase was found for Man5 in the reference, M5, and ST3 mAb experiments (Figure 5). Evidence has been presented linking this effect to interaction with mannose receptor.30