CD6 Antibody
Description
Introduction
CD6 Antibody refers to a class of immunoglobulins designed to target CD6, a transmembrane glycoprotein expressed predominantly on T cells, certain B cells, and natural killer (NK) cells. Its role spans immune activation, adhesion, and regulation of inflammatory responses, making it a focal point for therapeutic interventions in autoimmune diseases and cancer.
Immune Modulation
CD6 Antibodies modulate T cell responses by:
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Blocking Adhesion: Disrupting CD6-CD166 interactions, which are critical for immune synapse formation and leukocyte migration .
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Signaling Inhibition: Interfering with co-stimulatory signals that enhance T cell activation .
Therapeutic Targeting
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Antibody-Drug Conjugates (ADCs): CD6-ADCs deliver cytotoxic payloads (e.g., monomethyl auristatin E) selectively to activated T cells, sparing quiescent cells. This approach is effective in autoimmune uveitis and graft-versus-host disease (GVHD) .
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Immunosuppression: Monoclonal antibodies (e.g., MAB627) reduce T cell proliferation and cytokine production, used in organ/bone marrow transplant rejection .
Autoimmune Diseases
CD6 antibodies are investigated for:
Cancer and GVHD
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T Cell Lymphoma: CD6-ADCs eliminate malignant T cells while sparing normal cells .
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GVHD: Selectively depletes alloreactive T cells in humanized mouse models .
Preclinical Studies
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CD6-ADC: Demonstrated efficacy in autoimmune uveitis (90% reduction in inflammation) and GVHD (prolonged survival) .
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Biosafety: No significant toxicity observed in naive mice, with target-specific killing confirmed in HuT-78 T cells .
Clinical Relevance
Product Specs
Target Background
- This study demonstrates the involvement of CD6 in susceptibility to Behcet's disease in a Chinese Han population. PMID: 27108704
- These findings suggest that CD6 acts as a negative regulator of T-cell activation while simultaneously promoting activated T-cell survival, proliferation, and infiltration. This makes CD6 a potential target for treating multiple sclerosis (MS) and other T-cell-driven autoimmune conditions. PMID: 28209777
- This data supports a model where bivalent recruitment of a GADS/SLP-76 complex is necessary for costimulation by CD6. PMID: 28289074
- The research indicates that the T cell-specific adaptor protein (TSAd) SH2 domain interacts with CD6 antigen and linker for activation of T cells protein (LAT) phosphotyrosine (pTyr) peptides. PMID: 27896837
- Recent genetic association studies provide evidence for a role of CD6 in the pathogenesis of multiple sclerosis and rheumatoid arthritis. [review] PMID: 26844569
- This study sheds light on the role of CD6, a lymphocyte-specific surface receptor belonging to the ancient and highly conserved Scavenger Receptor Cysteine-Rich (SRCR) superfamily, as a pattern recognition receptor and its implications for T cell activation and differentiation. [review] PMID: 25777272
- The data highlights the multifaceted aspects that determine the signals transmitted via CD6 and the context that defines a dual role for this important T cell surface molecule. [review] PMID: 26028048
- The research demonstrates a role for extracellular and intracellular interactions of CD6 in lateral movement in response to T cell activation. [review] PMID: 26302795
- The binding sites on CD6 and CD166 have been characterized, revealing that a SNP in CD6 causes glycosylation which hinders the CD6/CD166 interaction. PMID: 26146185
- CD6 regulatory T cells are characterized by the expression of both CD6 and FOXP3. PMID: 25088497
- The interaction of Galectin-1 and -3 with CD6 has been investigated. PMID: 24945728
- Upon T cell activation, SRSF1 becomes limiting, and its function in CD6 exon 5 splicing is counteracted by an increase in CD6 transcription, dependent on chromatin acetylation. PMID: 24890719
- The CD6 polymorphism showed a reduced likelihood of optic neuritis as an attack location. PMID: 24130718
- In a Korean population, one SNP in CD6 was associated with neuromyelitis optica. PMID: 22994200
- This research reveals that a new MS-associated CD6 risk haplotype significantly alters the expression of CD6 on CD4(+) and CD8(+) T cells. PMID: 23638056
- A novel level of regulation of CD6 function by intracytoplasmic serine phosphorylation has been identified. PMID: 23711376
- The data suggests that genetic variations within CD6 and syntaxin binding protein 6 (STXBP6) may influence the response to TNFalpha inhibitors in patients with rheumatoid arthritis (RA). PMID: 22685579
- Cd6 acts as a signaling attenuator, and its expression alone, in the absence of ligand engagement, is sufficient to restrain signaling in T cells. PMID: 21956609
- These findings demonstrate that the multiple sclerosis risk allele in the CD6 locus is associated with altered proliferation of CD4(+) T cells. PMID: 21849685
- CD6 expression on peripheral NK cells identifies a novel CD56(dim) subpopulation associated with distinct patterns of cytokine and chemokine secretion. PMID: 21178331
- The association of single nucleotide polymorphisms with multiple sclerosis has been investigated. PMID: 21552549
- CD6+ B cells are reduced in Sjogren's syndrome. PMID: 20810246
- The data shows that CD6-ALCAM interaction in vitro induces a synergistic co-stimulation of normal peripheral blood mononuclear cells. PMID: 20726988
- This study strengthens the role of CD6 and TNFRSF1A as risk loci for multiple sclerosis, extending these findings to populations of southern European ancestry. PMID: 20430450
- CD6 associates with the scaffolding PDZ-containing protein syntenin-1 during the maturation of the immunological synapse. PMID: 16034076
- The engagement of CD6 with CD166 on tumor cells plays a significant role in gammadelta T cell activation by tumor cells sensitized with nonpeptide antigens endogenously or exogenously. PMID: 16818742
- The CD6-ALCAM interaction leads to the activation of three MAP kinase cascades, influencing the dynamic balance that determines whether resting or activated lymphocytes survive or undergo apoptosis. PMID: 16818773
- The costimulatory effect of CD6 is mediated through phosphorylation-dependent binding of a specific tyrosine residue, 662Y, in its cytoplasmic region to the adaptor SLP-76. PMID: 16914752
- The unprecedented bacterial binding properties of recombinant soluble CD6 support its therapeutic potential for the intervention of septic shock syndrome or other inflammatory diseases of infectious origin. PMID: 17601777
- A chimpanzee and human conserved CD6 domain 1 epitope recognized by T1 monoclonal antibody has been identified. PMID: 18707547
- Replication in an independent set of 2,215 subjects with multiple sclerosis (MS) and 2,116 control subjects validates new MS susceptibility loci at TNFRSF1A, IRF8, and CD6; TNFRSF1A harbors two independent susceptibility alleles. PMID: 19525953
- Comprehensive profiling of the cell surface proteome provides an effective approach for identifying commonly occurring proteins and proteins with restricted expression patterns in this compartment. PMID: 12493773
Q&A
What are the structural domains of CD6 relevant to antibody targeting?
CD6 is a type I membrane glycoprotein with three scavenger receptor cysteine-rich (SRCR) domains. Domain 1 (membrane-distal) contains two distinct epitopes recognized by monoclonal antibodies (mAbs):
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Epitope 1: Includes residue R77, targeted by mAbs like MT605 and T12.1.
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Epitope 2: Includes residue E63, targeted by mAbs like Itolizumab and MEM98 .
Domain 3 (membrane-proximal) binds CD166 (ALCAM), a ligand critical for T-cell adhesion and activation . Structural differences between domains influence antibody binding kinetics and functional outcomes .
How do CD6 antibodies modulate T-cell responses in autoimmune diseases?
CD6 antibodies primarily inhibit pathogenic T-cell activation through two mechanisms:
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Blocking CD6-ALCAM interactions: Domain 3-targeting mAbs disrupt adhesion between T cells and antigen-presenting cells (APCs), impairing immune synapse formation .
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Inhibiting signaling pathways: Domain 1 mAbs like Itolizumab reduce CD6 receptor hyper-phosphorylation, dampening ZAP70/SLP76 signaling .
Experimental Evidence:
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Itolizumab decreases Th17 differentiation and IL-17 production in in vitro Th17-polarizing conditions .
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In experimental autoimmune encephalomyelitis (EAE) models, anti-CD6 treatment reduces CNS inflammation and Th1/Th17 responses .
What are the key differences between CD6 domain 1 and domain 3 antibodies?
How do CD6 isoforms influence antibody efficacy in experimental models?
Alternative splicing generates two isoforms:
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Full-length CD6 (CD6WT): Contains all three domains, binds CD166.
Experimental Findings:
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CD6Δd3 mice show reduced autoimmune severity in EAE but impaired T-cell adhesion to APCs .
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Anti-CD6 mAbs targeting domain 1 (e.g., Itolizumab) retain efficacy in CD6Δd3 models, suggesting ligand-independent signaling inhibition .
What experimental approaches are used to evaluate CD6 antibody mechanisms?
What are the contradictions in CD6 antibody therapeutic effects across studies?
Key Contradictions:
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Dose-Dependent Effects:
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Dual Roles of CD6:
How does CD6 antibody treatment affect immune cell subsets in cancer?
CD6-targeted therapies exploit dual mechanisms:
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Depletion of Pathogenic T Cells:
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Enhancement of Antitumor Immunity:
Experimental Outcomes:
| Model | Treatment | Effect |
|---|---|---|
| Breast/Prostate Cancer | UMCD6 + Adoptive T cells | Increased tumor-infiltrating cytotoxic lymphocytes |
| T-Cell Lymphoma | CD6-ADC | Selective killing of malignant T cells |
What are the challenges in translating CD6 antibody therapies to humans?
What are the emerging applications of CD6 antibodies beyond autoimmunity?
Cancer Immunotherapy:
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CD6 CAR-T cells: Redirect Tregs to suppress alloreactivity .
Infectious Diseases: -
Sepsis: CD6−/− mice show reduced bacterial clearance, suggesting a role in innate immunity .
How do CD6 ligands (CD166, CD318) influence antibody therapeutic strategies?
Key Insight: Dual targeting of CD6 and its ligands may enhance therapeutic efficacy in autoimmune diseases and cancer .
