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Cutaneous Lymphomas
Published in Ayşe Serap Karadağ, Lawrence Charles Parish, Jordan V. Wang, Roxburgh's Common Skin Diseases, 2022
Emily Correia, Shalini Krishnasamy, Neda Nikbakht
Laboratory studies: ALCL on histology characteristically demonstrates sheets of large, nonepidermotropic, CD30+ atypical cells with anaplastic morphology in the dermis. Cells are round, oval, or have irregularly shaped nuclei, with prominent eosinophilic nucleoli and abundant cytoplasm. Cells may express the CD4+ phenotype and other T-cell markers, such as CD2, CD3, and CD5. Necrosis and ulceration with areas of more inflammatory cells may be seen and reactive lymphocytes are typically present at the periphery. Expression of anaplastic lymphoma kinase (ALK) and epithelial membrane antigen (EMA) on malignant cells should highly raise suspicion of systemic involvement of ALCL.
Biologic Therapies for Rheumatoid Arthritis
Published in Thomas F. Kresina, Monoclonal Antibodies, Cytokines, and Arthritis, 2020
Ian R. Mackay, Merrill J. Rowley, Claude C. A. Bernard
The CD3 molecular complex transduces activation signals after occupancy of the T cell antigen receptor. MAbs to CD3 have long been used successfully as anti-immune agents for attenuation of acute rejection of organ allografts—kidney, liver, or heart. Antibody to CD3 is not cytotoxic and appears to act by steric blockade of the T cell receptor for antigen. MAb to CD3 has not proven successful in the therapy of chronic immune-mediated disease, and the potential of anti-CD3 for total rather than selective immunosuppression requires that short-term courses be used in acute relapses. Hence anti-CD3 would not be judged as suitable for sustained systemic treatment of rheumatoid arthritis, although intrasynovial injection could be effective.
The Immune System During HIV-1 Infection
Published in Niel T. Constantine, Johnny D. Callahan, Douglas M. Watts, Retroviral Testing, 2020
Niel T. Constantine, Johnny D. Callahan, Douglas M. Watts
Several different cell determinations can help to define cellular immune status. Most often, these include quantitations for CD4+ T cells, CD8+ T cells, and sometimes CD2+ and CD3+ cells. In addition, the relative proportion of CD4+ to CD8+ cells (the T4/T8 or helper/suppressor ratio) can be a very valuable measurement. If a monoclonal antibody against CD4 is used, all T cells possessing this marker (i.e., Th and T inducer cells) will be identified. Likewise, CD8 monoclonals will identify T cytotoxic and T suppressor cells. Cells having the CD3 marker are all T cells considered to be immunocompetent (functioning properly). CD2+ cells represent the total number of T cells, regardless of their capability to function properly.
Structure-based engineering of a novel CD3ε-targeting antibody for reduced polyreactivity
Published in mAbs, 2023
Catherine Y Liu, Cory L Ahonen, Michael E Brown, Ling Zhou, Martin Welin, Eric M Krauland, Robert Pejchal, Paul F Widboom, Michael B Battles
T-cell stimulation is mediated by the T cell receptor (TCR)-CD3 complex with CD3 as the signaling component, where CD3 needs to be cross-linked to facilitate T-cell activation.7 Stimulation leads to early activation markers CD69 and CD25 being transcriptionally upregulated on the T-cell surface.8,9 These markers regulate the magnitude of the T cell proliferative response. Stimulation also causes the T cell to release pro-inflammatory cytokines such as IL-2, IFNγ, TNFα/β and others for Th1-biased cells. A growing body of literature suggests that CD3-targeting bispecific antibodies mimic the principles of kinetic segregation rooted in the mechanism of TCR/pMHC-mediated immunological synapse formation.10,11 The resulting TCR signaling coupled with cross-linking of cytotoxic CD8+ T-cells to targets cells expressing the TAA arm of the bispecific molecule can redirect cytotoxic effects toward the targeted cells.10–12
Liposomal T cell engager and re-director for tumor cell eradication in cancer immunotherapy
Published in mAbs, 2022
Fang Xie, Luchen Zhang, Sanyuan Shi, Anjie Zheng, Jiaxing Di, Shanshan Jin, Xuguang Miao, Fenglan Wu, Xiaolong Chen, Yanhong Zhang, Xiaohui Wei, Yuhong Xu
In order to construct and combine the different immunomodulatory components, we describe here the development and optimization of T cell Redirecting Antibody Fragment-anchored Liposomes (TRAFsomes). Antibody fragments were anchored onto liposomal surfaces for interaction with various cell surface receptors.10 Such a format enabled multivalent and multispecific interactions and resulted in T cell engagement and cancer cell lysis. Several reports have described similar nano-sized liposomes or nanoparticles coated with anti-CD3, anti-CD40, anti-4-1BB, anti-PD-1, or anti-LAG-3,11–14 but specific details about their immune-modulation effects are lacking, especially in reference to TDBs. We examined TRAFsomes with varying stoichiometries of anti-CD3 and anti-CD19 Fab’ and compared their binding and T cell engaging properties. The results were analyzed to understand the unique immune modulation aspects of TRAFsomes as compared to those reported in blinatumomab studies. The liposome pharmacokinetic properties and various temporal features of T cell subsets activation were analyzed. Furthermore, we showed that TRAFsomes encapsulating certain doses of dasatinib exerted biased modulation of CD8 + T cells before inhibiting all T cell activities at higher doses. An in vivo study demonstrated how the multiplicity of CD3 engagement may affect the resulting T cell activities and immunotherapy outcomes. These understandings are crucial for developing TRAFsomes as a new TDB format for cancer treatment.
Impact of Proinflammatory Cytokine Gene Polymorphisms and Circulating CD3 on Long-Term Renal Allograft Outcome in Egyptian Patients
Published in Immunological Investigations, 2021
Sabah Farouk El-Abd, Nagwa Mansour Badr Eldin, Salwa Mahmoud Elwasif, Nora Abdel Sameaa Ahmed, Eman Salah El-Shafey, Eslam Elsherbiny
The CD3 is a T cell receptor which serves as an activator for the cytotoxic T cell (CD8+ naive T cells) and T helper cells (CD4+ naive T cells). Initial expression of CD3 place in the cytoplasm in a peri-nuclear location of pro-thymocytes. During maturation of T cell, the loss of cytoplasmic CD3 expression occur accompanied with the presence of the CD3 antigen on the cell surface (Smith-Garvin et al. 2009). T-lymphocytes are demonstrated to be involved in acute allograft rejection. T cell receptor (TCR), CD-3, CD-4, or CD-8 receptors play an important role in antigen recognition and T-cell activation. TCR/CD-3 and CD-4 recognize antigen in combination with major histocompatibility complex (MHC) class II, TCR/CD-3 and CD-8 recognize antigen in combination with MHC class I molecules (Grunewald et al. 2000). The innovation of a modified analysis staining technique for detection of CD3+ T-cell density could give potential results to determine the rejection severity than traditional methods along with visual assessment (Moon et al. 2018).