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Transplantation
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Jonathon Olsburgh, Rhana H. Zakri
BelataceptSoluble fusion protein.Selectively inhibits CD28-mediated co-stimulation of T-cells.Fusion protein with natural binding properties: CTLA-4-Ig (LEA29Y).Limited to clinical trials – explore novel IS regimes to minimise CNI use/toxicity.
Active Specific Immunization by the Use of Leukemic Dendritic Cell Vaccines
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Ilse Houtenbos, Gert J. Ossenkoppele, Arjan A. van de Loosdrecht
A second signal termed costimulation is crucial for final T-cell activation. Absence of this second activation signal can lead to T-cell anergy with subsequent tolerance to the presented antigen. A number of molecular interactions contribute to costimulatory signaling. CD28 is the most important costimulatory molecule expressed on naïve T cells and interacts with CD80 and CD86 on APC. Upon activation, T cells will proliferate and differentiate towards effector and memory subtypes. Additionally, T cells upregulate the expression of other costimulatory molecules with either a stimulatory or inhibitory function thereby regulating the immune response.
Immunotherapy
Published in Prakash Srinivasan Timiri Shanmugam, Understanding Cancer Therapies, 2018
Sowmiya Renjith, Sathya Chandran
Cancers can modulate through a variety of mechanisms, which are not very well understood, to suppress or prevent attack by immune cells. The most distinguishable example is through expression of PD-L1. Immune checkpoints, such as the PD1 pathway, are part of a protein-ligand receptor system that modulates T-cell activation. They are vital for protecting self-tolerance and controlling the duration and amplitude of physiologic immune response, but are changed by the tumor to initiate tumor growth that is hidden by the immune system. In a normal cell, when PD-L1 or PD-L2 combines with PD1, the T cell becomes inactive. This is one of the ways that the host regulates the immune system to avoid an overreaction. Nevertheless, PD-L1 is also exhibited in HNSCC, leading to the disarming of T cells after binding to PD1 on T cells (Tsushima et al. 2006). The concentration of TILs is contrast in association with PD-L1 expression of tumor cells (Cho et al. 2011). CTLA-4 is another immune checkpoint located on the surface of activated CTLs that combines to the B7 ligands found on APCs. T cells have a CD28 receptor that represents a stimulatory counterpart to CTLA4, causing T-cell activation. CTLA-4 competes with the CD28 receptor for binding to the B7 ligand, leading to either an inhibitory or stimulatory effect on T cells (Pardoll 2012).
Advances in pharmacotherapy for acute kidney injury
Published in Expert Opinion on Pharmacotherapy, 2022
Yali Xu, Ping Zou, Xiaojing Cao
CD28 is a costimulatory molecule that activates T lymphocytes. Superantigen toxins can directly bind to the CD28 receptor to induce the expression of the inflammatory cytokinine gene, and inhibit the plasma reduction of tumor necrosis factor α, interleukin-2 (IL-2), IL-4, IL-6, IL-10, interferon γ, and monocyte chemoprotein 1 (MCP-1) levels, thereby improving renal failure in sepsis model animals [28]. Preclinical trials have shown that selective block of the CD28 receptor reduces systemic inflammatory response. Reltecimod (also AB103 or p2TA) is a CD28 receptor antagonist that reduces bacterial binding of superantigen protein to CD28 on T cells, thus reducing the release of multiple proinflammatory cytokines, inflammatory response in patients and finally decreasing the incidence of AKI [29]. A phase III clinical trial is ongoing to assess the efficacy and safety of reltecimod in patients with sepsis-associated Stage 2/3 AKI (NCT03403751) [30].
Association of Rs231775 Genetic Variant of Cytotoxic T-lymphocyte Associated Protein 4 with Alopecia Areata Disease in Males: A Case–Control Study
Published in Immunological Investigations, 2021
Nader Ali Ismail, Eman Ali Toraih, Hatem Mohamed Ameen, Amal Hussein Ahmed Gomaa, Radwa El- Sayed Mahmoud Marie
Genome-wide association studies identified eight regions associated with AA. One locus that encloses Cytotoxic T-lymphocyte Associated Protein 4 (CTLA4 gene) was determined at chromosome 2 (2q33-34) (Petukhova et al. 2010). CTLA4 gene encodes a glycoprotein receptor of the immunoglobulin family expressed on the surface of activated T cells (Kolar et al. 2009). CTLA 4 negatively regulates T-cell activation. It is homologous to the T-cell co-stimulatory protein, CD28. CTLA4 binds B7-1 and B7-2 on antigen-presenting cells with greater affinity and avidity than CD28 thus blocking CD28 for its ligands. CTLA4 transmits an inhibitory signal to T-cells (Chaitra et al. 2010). Thus, it effectively turns off the excessive and unnecessary immune response to protect against autoimmunity (Dong et al. 2014).
Research progress in tumor targeted immunotherapy
Published in Expert Opinion on Drug Delivery, 2021
Yuelin Fang, Aihua Yu, Lei Ye, Guangxi Zhai
CTLA-4/CD152 is the first clinically targeted immune checkpoint receptor; however, the mechanisms of CTLA-4 remain obscure. Primarily, CTLA-4 inhibits T cell activity by competing with the co-stimulatory receptor CD28 on T cells. Once antigen recognition occurs, the CD28 signal strongly amplifies the TCR signal to activate T cells. CTLA-4 and CD28 have the same ligands CD80 (B7-1) and CD86 (B7-2), but CTLA-4 has a higher affinity for both ligands, thereby preventing the B7 molecule from interacting with the co-stimulatory molecule CD28 [120]. PD-1 (CD279) is a prominent immune checkpoint receptor on the surface of T cells, and PD-L1 (B7-H1/CD274) is mainly expressed on cancer cells. PD-1 combined with PD-L1 negatively regulates T-cell function by inhibiting the kinase signaling pathway. Besides the two major kinds of immunological checkpoint receptors, indoleamine 2,3-dioxygenase (IDO) also has high expression levels in tumor tissues to inhibit the proliferation of T cells and accelerate the migration rate of the tumor. IDO exerts its immunosuppressive effect by catabolizing tryptophan into kynurenines and promoting the conversion of naive T cells to Treg cells. Currently, the most widely used IDO inhibitor is 1-methyl-DL-tryptophan (1-MT) [121].