The immunological function of CD52 and its targeting in organ transplantation

Zhao, Yang; Su, H.; Shen, Xiaofei; Du, Jun; Zhang, Xiaodong; Zhao, Yong

doi:10.1007/s00011-017-1032-8

Cited by 86 publications

(71 citation statements)

References 102 publications

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“…Anti-CD52 (alemtuzumab, lemtrada R ) is instead a humanized IgG1 monoclonal antibody (mAb) that eliminates CD52-expressing lymphocytes and generates a marked lymphopenia. Administration of this depleting mAb has been employed clinically for the treatment of lymphoma [3], the prevention of transplant rejection [4][5][6], and more recently it has been shown to efficiently inhibit relapses in MS patients [7,8]. CD52 is highly expressed on the surface of T and B lymphocytes and to a lesser extent on NK cells, monocytes, macrophages, DCs, eosinophils, and neutrophils [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…CD52 is highly expressed on the surface of T and B lymphocytes and to a lesser extent on NK cells, monocytes, macrophages, DCs, eosinophils, and neutrophils [9][10][11][12][13]. Although the function of CD52 on immune cells is still unclear, some evidence suggests that it may modulate T-cell activation and induce regulatory CD4 T cells [6]. Activated CD4 T cells with higher CD52 expression were able to suppress other effector T cells [14].…”

Section: Introductionmentioning

confidence: 99%

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Anti‐CD52 blocks EAE independent of PD‐1 signals and promotes repopulation dominated by double‐negative T cells and newly generated T and B cells

et al. 2020

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Lymphocyte depletion using anti‐CD52 antibody effectively reduces relapses of multiple sclerosis (MS). To begin to understand what mechanisms might control this outcome, we examined the effect of a murine‐CD52‐specific mAb on the depletion and repopulation of immune cells in mice with experimental autoimmune encephalomyelitis (EAE), a model of MS. We tested whether the tolerance‐promoting receptor programmed cell death protein‐1 (PD‐1) is required for disease remission post anti‐CD52, and found that PD‐1‐deficient mice with a more severe EAE were nevertheless effectively treated with anti‐CD52. Anti‐CD52 increased the proportions of newly generated T cells and double‐negative (DN) T cells while reducing newly generated B cells; the latter effect being associated with a higher expression of CD52 by these cells. In the longer term, anti‐CD52 caused substantial increases in the proportion of newly generated lymphocytes and DN T cells in mice with EAE. Thus, the rapid repopulation of lymphocytes from central lymphoid organs post anti‐CD52 may limit further disease. Furthermore, these data identify DN T cells, a subset with immunoregulatory potential, as a significant hyperrepopulating subset following CD52‐mediated depletion.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti‐CD52 blocks EAE independent of PD‐1 signals and promotes repopulation dominated by double‐negative T cells and newly generated T and B cells

et al. 2020

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“…Studies have shown that Siglec-10 plays an important role in regulating the immune balance of in ammatory diseases. For example, the interaction of Siglec-10 and CD24 reduces the in ammatory response associated with the damage-associated molecular patterns (DAMPs) by inhibiting the activation of high mobility group box 1 (HMGB1) and NF-κB [15][16][17][18]. The interaction between Siglec-10 expressed on human DC and pseudaminic acid can increase the expression of IL-10 through MyD88 and p38 MAPK signaling pathway to promote anti-in ammatory function [19].…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Long-term Elevated Siglec-10 in Cerebral Spinal Fluid Heralds Better Prognosis for Patients with Aneurysmal Subarachnoid Hemorrhage

S¹,

Peng²,

Chen³

et al. 2020

Preprint

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Background The presence of aneurysmal subarachnoid hemorrhage (aSAH) is usually accompanied by excessive inflammatory response leading to the destruction of central nervous system, while the sialic acid-binding Ig-like lectin 10 (Siglec-10) is a factor recognized as having the ability to modify the inflammatory microenvironment, indicating a potential protective effect in aSAH. Methods We collected the cerebrospinal fluid (CSF) of control group and aSAH patients at different time points, measured the Siglec-10 concentration by the enzyme-linked immunosorbent assay (ELISA), and evaluated the changes of Glasgow Outcome Scale (GOS) and Glasgow Coma Scale (GCS) in the disease progression. Results Our data showed that the Siglec-10 level in CSF could respond to aSAH and quickly rose to a peak, then fell back to a stable range slightly higher than the normal range. Severely impaired patients were likely to maintain high levels of Siglec-10 for longer periods. Generally, having high-level and long-term Siglec-10 indicated a better prognosis. Conclusions These results suggested that Siglec-10 could possibly reduce the degree of inflammatory response related to the damage-associated molecular patterns (DAMPs) by regulating the balance between pro-inflammatory and anti-inflammatory, thereby improving the patient's prognosis. These findings might provide new treatment perspectives for aSAH and other inflammation-related diseases.

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“…Virtually all T-PLL express CD52 and at a higher density than in other T cell and B cell malignancies [27]. Engagement of CD52 by alemtuzumab induces antibody-dependent cytolysis, activation of the complement system, and possibly direct apoptosis [28,29].…”

Section: Alemtuzumab Remains the Current Benchmarkmentioning

confidence: 99%

Advances and Perspectives in the Treatment of T-PLL

Braun

Jan

Wahnschaffe

et al. 2020

Curr Hematol Malig Rep

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Purpose of Review T cell prolymphocytic leukemia (T-PLL) is a rare mature T cell tumor. Available treatment options in this aggressive disease are largely inefficient and patient outcomes are highly dissatisfactory. Current therapeutic strategies mainly employ the CD52-antibody alemtuzumab as the most active single agent. However, sustained remissions after sole alemtuzumabbased induction are exceptions. Responses after available second-line strategies are even less durable. More profound disease control or rare curative outcomes can currently only be expected after a consolidating allogeneic hematopoietic stem cell transplantation (allo-HSCT) in best first response. However, only 30-50% of patients are eligible for this procedure. Major advances in the molecular characterization of T-PLL during recent years have stimulated translational studies on potential vulnerabilities of the T-PLL cell. We summarize here the current state of "classical" treatments and critically appraise novel (pre)clinical strategies. Recent Findings Alemtuzumab-induced first remissions, accomplished in ≈ 90% of patients, last at median ≈ 12 months. Series on allo-HSCT in T-PLL, although of very heterogeneous character, suggest a slight improvement in outcomes among transplanted patients within the past decade. Dual-action nucleosides such as bendamustine or cladribine show moderate clinical activity as single agents in the setting of relapsed or refractory disease. Induction of apoptosis via reactivation of p53 (e.g., by inhibitors of HDAC or MDM2) and targeting of its downstream pathways (i.e., BCL2 family antagonists, CDK inhibitors) are promising new approaches. Novel strategies also focus on inhibition of the JAK/STAT pathway with the first clinical data. Implementations of immune-checkpoint blockades or CART cell therapy are at the stage of pre-clinical assessments of activity and feasibility. Summary The recommended treatment strategy in T-PLL remains a successful induction by infusional alemtuzumab followed by a consolidating allo-HSCT in eligible patients. Nevertheless, long-term survivors after this "standard" comprise only 10-20%. The increasingly revealed molecular make-up of T-PLL and the tremendous expansion of approved targeted compounds in oncology represent a "never-before" opportunity to successfully tackle the voids in T-PLL. Approaches, e.g., those reinstating deficient cell death execution, show encouraging pre-clinical and first-inhuman results in T-PLL, and urgently have to be transferred to systematic clinical testing.

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The immunological function of CD52 and its targeting in organ transplantation

Cited by 86 publications

References 102 publications

Anti‐CD52 blocks EAE independent of PD‐1 signals and promotes repopulation dominated by double‐negative T cells and newly generated T and B cells

Anti‐CD52 blocks EAE independent of PD‐1 signals and promotes repopulation dominated by double‐negative T cells and newly generated T and B cells

WITHDRAWN: Long-term Elevated Siglec-10 in Cerebral Spinal Fluid Heralds Better Prognosis for Patients with Aneurysmal Subarachnoid Hemorrhage

Advances and Perspectives in the Treatment of T-PLL

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