Alefacept, Recombinant human LFA3 protein, Fc tagged
Alefacept, Immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 (LFA-3/LFA3) linked to the Fc portion of human IgG1. Expressed in CHO cells, MW is 91.4 kD.
<0.001 EU per 1 μg of the peptide by the LAL method
Lyophilized protein should be stored at < -20°C, though stable at room temperature for 3 weeks. Reconstituted protein solution can be stored at 2-8 °C for 1 week. Aliquots of reconstituted samples are stable at < -20°C for 3 months.
As an immunosuppressive drug, The product can be used for treatment of moderate to severe chronic plaque psoriasis.
Examples of Clinical Use:
Moderate to severe chronic plaque psoriasis
Interferes with lymphocyte activation by specifically binding to the lymphocyte antigen, CD2, and inhibiting LFA-3/CD2 interaction. Activation of T lymphocytes involving the interaction between LFA-3 on antigen-presenting cells and CD2 on T lymphocytes plays a role in the pathophysiology of chronic plaque psoriasis. Also causes a reduction in subsets of CD2+ T lymphocytes as well as CD4+ and CD8+ T lymphocytes.
Mechanism of action:
Inhibits T-lymphocyte activation and production by binding to the CD2 lymphocyte antigen.
Humans and other mammals
Target 1. T-cell surface antigen CD2; Target 2. Complement C1r subcomponent; Target 3. Complement C1q subcomponent subunit A; Target 4. Complement C1q subcomponent subunit B; Target 5. Complement C1q subcomponent subunit C; Target 6. Low affinity immunoglobulin gamma Fc region receptor III-A; Target 7. High affinity immunoglobulin gamma Fc receptor I; Target 8. Low affinity immunoglobulin gamma Fc region receptor II-a; Target 9. Low affinity immunoglobulin gamma Fc region receptor II-b; Target 10. Low affinity immunoglobulin gamma Fc region receptor II-c; Target 11. Low affinity immunoglobulin gamma Fc region receptor III-B
The Lymphocyte function-associated antigen 3 (LFA3) is a capture molecule initially cloned in 1984. It owes its discovery to Kishimoto's team who observed its presence on all human peripheral blood lymphocytes. This cell adhesion protein, also known as CD58, is found encoded inside the gene locus on chromosome 1 at segment 1p13. This compact site facilitates its biochemical workings, which involve initiating molecular signals via a networked cellular pathway.
Understanding the structure of the LFA3 protein is essential in realizing its key role in fostering cell-cell interactions. Located on the outer surfaces of cells, this glycan-containing protein has an extracellular domain housing two to four Ig-like domains, a hydrophobic transmembrane region, and a short cytoplasmic tail.
Function of LFA3 Protein
LFA3 protein functions primarily in facilitating adhesion between cells, playing a pivotal role in various immunological reactions. It modulates hematopoietic cell adhesion and T cell antigen recognition. It plays a crucial role in the active participation and response of the immune system by facilitating interactions between T-cells and antigen-presenting cells (APCs). It binds to its receptor, CD2, found on the surface of T-cells, and critically influences T-cell activation and regulatory functions.
Signaling Pathways Related to LFA3
Signal transduction within cells is facilitated by LFA3, specifically through the immunological synapse architecture. Various signaling pathways are also centered around its action. The binding of LFA3 to CD2 stimulates the CD2/LFA3 signaling pathway that fosters cytoskeletal rearrangement and increases cell adhesion, essential for T cell-target cell conjugation. Moreover, this interaction stimulates the Ras-Erk pathway, a signaling route significant in cell survival, proliferation, and differentiation to help maintain a balanced immune response.
LFA3 and Related Diseases
Abnormal function or expression of the LFA3 protein can lead to various diseases, particularly among autoimmune and infectious diseases. For instance, Multiple Sclerosis (MS), a chronic autoimmune, inflammatory neurological disease of the central nervous system, involves a dysregulated immune response. Increased levels of soluble LFA3 have been noted in MS patients, indicating its potential as a biomarker.
Interferon beta-1a, a drug utilized in treating relapsing forms of multiple sclerosis, has shown the ability to modulate the immune response. Research indicates that it reduces the production and activity of pro-inflammatory cytokines and increases anti-inflammatory cytokines. This switch in cytokine balance by Interferon beta-1a can potentially regulate the expression of LFA3, influencing the pathogenesis of the disease.
Applications of LFA3 in Medicine
The LFA3 protein, owing to its immune response regulating properties, has extensive applications in therapeutic settings. For example, Alefacept, an LFA3-Ig fusion protein, is used to inhibit the activation of T cells in the treatment of moderate to severe psoriasis. The drug inhibits the activation of memory-effector T lymphocytes by blocking the interaction of LFA3 with CD2.
Drug Candidates Related to LFA3
Apart from Alefacept, other drug candidates related to LFA3 are under evaluation. A promising avenue is the development of LFA3 protein-based cancer immunotherapies. Some potential drug candidates in this category include CAT-8015, a recombinant biotherapeutic protein, which retargets existing CD2 on effector T cells to CD22 expressed cells in hematological malignancies.
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without prior written approval from Creative BioMart.
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