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Immune System Imaging
Published in Margarida M. Barroso, Xavier Intes, In Vivo, 2020
Michael J. Hickey, M. Ursula Norman
Leukocyte migration is typically driven by interaction of chemokines with leukocyte-expressed chemokine receptors. In the cortex, chemokine expression is relatively low and uniform with CCL25 and CXCL12 contributing to DN thymocyte accumulation at the SCZ (Plotkin et al., 2003; Bunting et al., 2011; Dzhagalov and Phee, 2012). In the medulla, both the CCR4 ligands (CCL17, CCL22) and the CCR7 ligands (CCL19, CCL21) are highly expressed by medullary DCs, setting up a chemotactic gradient to attract cells expressing the appropriate receptors. After positive selection, thymocytes upregulate CCR4 and CCR7 allowing these cells to migrate into the medulla in response to this chemotactic gradient (Misslitz et al., 2006; Petrie and Zuniga-Pflucker, 2007). 2PM studies show that this migration is blocked by an inhibitor of chemokine receptor signaling. Similarly, positively selected thymocytes deficient in CCR7 showed reduced entry into the medulla following positive selection (Kurobe et al., 2006; Ehrlich et al., 2009), while CCR4 deficiency also reduced the ability of postpositive selection DP and SP CD4 thymocytes to accumulate in the medulla and to interact with medullary DCs (Hu et al., 2015). Together these observations support a role for chemokine-driven migration in these responses.
Gene Therapy and Gene Correction
Published in Yashwant V. Pathak, Gene Delivery Systems, 2022
Manish P. Patel, Sagar A. Popat, Jayvadan K. Patel
ZFNs have targeted many plants, animals, flies, fish and various mammalian cell lines for genome engineering. ZFNs also have the useful advantage of generation of mutation as same as organism, which can be used as model for further study. ZFNs were also evaluated as a possible cure for HIV infection. C chemokine receptor 5 (CCR5) is a promising target for the control of HIV entry, as HIV requires expression of a co-receptor of CCR5 for adhesion to T cells (Maier et al. 2013). ZNFs were tested in an attempt to disrupt CCR5 in CD4+ human T cells and human hematopoietic stem cells. A phase 1 clinical trial in humans was concluded evaluating the ZNF approach for HIV treatment (Holt et al. 2010; Perez et al. 2008).
Nanoprobes for Early Diagnosis of Cancer
Published in Klaus D. Sattler, st Century Nanoscience – A Handbook, 2020
Chemokine receptors (CCRs) and their ligands regulate cell motility, invasiveness, and survival. In some tumors, the expression of CCRs (e.g., CCR5) is upregulated and is associated with promoted cancer progression. Therefore, CCR5 can be a useful biomarker for the early detection of cancer. To image CCR5, Xia and colleagues developed DAPTA (aSTTTNYT)-modified PdCu@Au core–shell tripods.35 The CCR5 expression in 4T1 tumors can be visualized using a radiolabeled version of the nanoprobe, DAPTAPd64Cu@Au, with higher uptake and tumor-to-muscle accumulation ratios compared to non-targeted nanoprobes and free DAPTA-blocked nanoprobes (Figure 8.5).
Peptide-enabled receptor-binding-quantum dots for enhanced detection and migration inhibition of cancer cells
Published in Journal of Biomaterials Science, Polymer Edition, 2020
Ruijuan Zu, Xiaocui Fang, Yuchen Lin, Shilin Xu, Jie Meng, Haiyan Xu, Yanlian Yang, Chen Wang
Dedicated efforts have been reported on studying chemokine receptor CXCR4 as a potential therapeutic target for cancer diagnosis and treatment [10]. One small molecule antagonist named as plerixafor (also termed as AMD3100) has been approved by the U.S. Food and Drug Administration (FDA) for non-Hodgkin’s lymphoma and multiple myeloma treatment [11,12]. Several other CXCR4 antagonist candidates are currently being evaluated in various stages of clinical development. In our previous study, we selected a series of potential peptide antagonists with designated sequences in our original experiments according to the extracellular domain of CXCR4. The binding strengths between peptide antagonists and CXCR4 were examined using flow cytometry, surface plasmon resonance (SPR), and confocal microscopy methods. Our results demonstrated that, peptide E5 (GGRSFFLLRRIQGCRFRNTVDD) shows high binding affinity and selectivity towards CXCR4-overexpressed cancer cells [13]. E5 was observed to inhibit the migration and adhesion of cancer cells, and increase the sensitivity of cancer cells to chemotherapeutic agents by antagonizing CXCR4/CXCL12 chemokine axis [13–15].