CD6 Specific Neutra™ Antibody Products

CD6 is a signal-transducing transmembrane receptor predominantly expressed on all T cells, and also found on subsets of B cells and NK cells. It engages with various endogenous ligands, including CD166/ALCAM, CD318/CDCP-1, and Galectins 1 and 3, which are often overexpressed by malignant cells in various cancers. The presence of CD6 on multiple immune cells and its interaction with these ligands make it an attractive target for new cancer immunotherapies. These therapies may involve classical approaches using monoclonal antibodies, innovative strategies such as soluble recombinant decoys, or the adoptive transfer of immune cells modified with chimeric antigen receptors. The potential of CD6 in enhancing cancer treatment stems from its role in modulating immune responses, thereby offering pathways to both potentiate and regulate anti-tumor activity.

Its Gene ID: 923, UniProtKB ID: P30203, OMIM ID: 186720

The Structure and Ligands of CD6

CD6 is a type I transmembrane glycoprotein, weighing 105–130 kDa, and belongs to the Scavenger Receptor Cysteine-Rich (SRCR) superfamily. It features three SRCR domains in its extracellular region, a transmembrane segment, and a cytoplasmic tail with no intrinsic catalytic activity but contains phosphorylatable residues for signal transduction. Expressed in T cells, certain B and NK cell subsets, hematopoietic precursors, and parts of the central nervous system, CD6 also has a soluble form produced via proteolytic cleavage after T-cell activation. CD6 interacts with several ligands, the most well-known of which is CD166/ALCAM (Activated Leukocyte Cell Adhesion Molecule). This interaction is critical for the stabilization of the immunological synapse during T cell responses. Other reported ligands for CD6 include CD318/CDCP1 and galectins, such as Galectin-1 and Galectin-3, which contribute to various signal transduction pathways influencing immune cell behavior.

Fig.1 The CD6 Structure and CD6-CD166/ALCAM Interactions.¹

The Function of CD6

CD6 is intricately involved in modulating T cell responses through its association with the TCR/CD3 complex. It stabilizes adhesive contacts with antigen-presenting cells at the immunological synapse, influencing proliferative and differentiation responses in T cells. Although initial studies suggested a co-stimulatory role for CD6, enhancing T cell activation, later research identified it as a potential negative modulator. CD6 impacts T cell activity by interacting with various intracellular signaling molecules and adaptors, thus influencing calcium mobilization and other signaling pathways. In CD6-deficient mice, altered immune responses highlight CD6's role in modulating TCR/CD3 signaling, which can vary depending on the immune context and experimental conditions. This multifunctionality makes CD6 a critical player in both promoting and regulating immune responses, reflecting its complex role in immune cell signaling and interaction with its ligands.

Cancer Immunotherapy Strategy Based on CD6

• Depleting and Non-Depleting Anti-CD6 mAb-Based Strategies

Recent studies have explored the therapeutic potential of a humanized anti-CD6 monoclonal antibody (UMCD6 mAb) in treating T-cell lymphoma. This antibody, when conjugated to a toxin (monomethyl auristatin E), selectively targets and destroys CD6-positive lymphoma cells without harming normal human cells. This approach showed significant tumor reduction in pre-clinical mouse models. Additionally, UMCD6 enhanced the anti-tumor effects of human immune cells against various cancer types in both in vitro and in vivo models, surpassing some current immune checkpoint inhibitors.

• CD6 Decoy Receptor-Based Strategies

Soluble proteins such as decoy receptors are effective in blocking receptor-ligand interactions, widely used in treating inflammatory disorders and cancer. The human CD6 soluble form (shCD6) appears at low concentrations in healthy individuals but is elevated in those with inflammatory conditions. It mimics the extracellular region of CD6, inhibiting T-cell proliferation in vitro, suggesting its potential as an immunomodulatory agent. Preclinical studies indicate shCD6 reduces tumor growth and impacts immune responses, with potential therapeutic applications without inducing autoimmune side effects.

• Adoptive Immune Cell Transfer-Based Strategies

Exploring the use of the extracellular region of human CD6 as an antigen-binding domain for CAR T-cell therapy shows promise, particularly against cancers with high CD166/ALCAM expression. This approach could target a broad spectrum of tumors but exhibits specificity primarily to CD166/ALCAM, not affecting cells expressing low levels of this ligand. Early studies indicate potent anti-tumor effects, especially against cancer stem cells, suggesting potential for targeted therapy with reduced off-tumor toxicity.

Fig.2 Cancer Immunotherapy Strategy Based on CD6.¹

Creative Biolabs is dedicated to offering superior one-stop services and products focused on CD6, a critical component in immunotherapy and cancer research. Leveraging our advanced neutralizing and recombinant antibody technologies, we provide high-quality, tailored solutions that encompass a range of CD6-targeted research and diagnostic tools. Our commitment to excellence ensures that our clients receive the most effective and innovative CD6-related applications to advance their research and clinical goals.

REFERENCE

1. Aragón-Serrano, Lucía, et al. "CD6 and Its Interacting Partners: Newcomers to the Block of Cancer Immunotherapies." International Journal of Molecular Sciences 24.24 (2023): 17510.