CD6 modulates T-cell activation, adhesion, and survival through interactions with its ligands:
Co-stimulatory/Co-inhibitory Signaling:
Adhesion: Facilitates T-cell binding to CD166-expressing endothelial and antigen-presenting cells .
Cancer Immunity: CD6 ligands (e.g., CD318) on tumor cells enable antibody-mediated cytotoxicity via NK and CAR-T cells .
CD6-deficient mice show reduced autoimmune severity (e.g., experimental autoimmune encephalomyelitis) due to impaired T-cell survival and cytokine production .
Antibodies like itolizumab (anti-CD6D1) inhibit IL-17 production and STAT3/RORγT pathways in Th17 cells .
CD6 antibodies are therapeutic candidates for conditions driven by Th1/Th17 dysregulation:
Itolizumab reduced mortality in severe COVID-19 by:
Different clones target distinct CD6 domains, altering functional outcomes:
Cancer: CD6-augmented CAR-T cells eliminated colorectal cancer stem cells in murine models .
Multiple Sclerosis: Anti-CD6 antibodies reduced spinal cord T-cell infiltration by 60% in EAE models .
Dual Signaling: CD6’s role as both activator and inhibitor complicates therapeutic targeting .
Ligand Diversity: CD6 interacts with CD166, CD318, and CD44, necessitating context-specific antibody design .
Clinical Trials: Ongoing studies focus on optimizing dosing and combination therapies (e.g., with corticosteroids for GVHD) .
Antibodies targeting specific immune receptors and complement proteins have become critical tools in both basic research and therapeutic development. Below is a structured FAQ addressing key scientific considerations for researchers working with antibodies like those targeting CCR6, C6, or LY6G6D, synthesized from peer-reviewed studies and patent literature.
Case example: CCR6+ T cell migration assays
Condition | CCL20 (100 ng/mL) | Anti-CCR6 Ab (10 μg/mL) | Migration Inhibition |
---|---|---|---|
Transwell assay | 1500 ± 212 cells | 287 ± 54 cells | 81% |
In vivo imaging | 12.3 mm² area | 4.1 mm² area | 67% |
Resolution strategy:
Validate chemotaxis gradient stability using microfluidic devices
Compare multiple detection methods (e.g., fluorescent dye vs. luciferase labeling)
Control for Fc receptor-mediated artifact migration using F(ab')₂ fragments
For anti-LY6G6D bispecific antibodies:
Phylogenetic analysis of LY6 protein family conservation (73% homology LY6G6D/G6F)
Molecular docking simulations using RosettaAntibody to identify paratope-epitope clashes
SPR validation against recombinant LY6 paralogs (KD >1 μM acceptable)
Anti-C6 antibody in EAE model:
Dose (mg/kg) | CSF Penetration (%) | Disease Onset Delay (days) | Relapse Rate |
---|---|---|---|
10 | 0.8 | 4.2 ± 1.1 | 63% |
30 | 2.1 | 8.9 ± 2.3 | 27% |
Key considerations:
Cerebrospinal fluid sampling at multiple timepoints
Parallel measurement of peripheral MAC activity
Critical validation steps for research antibodies:
Batch consistency testing
Stability profiling
Orthogonal functional assays