CCD4 Antibody

Definition and Biological Relevance

CD4 is a glycoprotein co-receptor on helper T cells, monocytes, macrophages, and dendritic cells. It binds MHC class II molecules during antigen presentation and recruits the tyrosine kinase Lck to amplify T-cell receptor (TCR) signaling . CD4 antibodies target this protein to modulate immune responses, with applications in autoimmune diseases, viral infections, and hematopoietic stem cell transplantation (HSCT).

Key CD4 Antibodies and Their Properties

The following table highlights notable CD4 antibodies, their mechanisms, and applications:

Autoimmune Diseases

• Rheumatoid Arthritis (RA):

  • MAX.16H5 reduced ESR, CRP, and joint inflammation in clinical trials .

  • Combined with chlorambucil, it improved clinical outcomes in refractory RA .

• Crohn’s Disease:

  • cM-T412 (chimeric anti-CD4) showed moderate efficacy (25–36% reduction in CDAI scores) but limited endoscopic improvement .

• Multiple Sclerosis (MS):

  • cM-T412 reduced CD4+ T cells but showed no significant MRI lesion reduction; efficacy correlated with depletion levels .

HIV Treatment

• N6 neutralizes 98% of HIV isolates, including strains resistant to other CD4-binding antibodies. Its broad activity stems from tolerance to viral mutations and avoidance of glycan clashes .

Hematopoietic Stem Cell Transplantation (HSCT)

• MAX.16H5 blocks graft-vs.-host disease (GVHD) ex vivo by binding CD4+ T cells in HSCT grafts, preserving graft-vs.-leukemia (GVL) effects .

Mechanisms of Action

1. Helper Function Disruption:

   • CD4 antibodies inhibit TCR-MHC II interactions, reducing B-cell activation and antibody production .

2. Direct Cytotoxicity:

   • Depleting antibodies (e.g., cM-T412) eliminate CD4+ T cells, suppressing autoimmune responses .

3. Viral Neutralization:

   • N6 binds HIV Env’s CD4-binding site, blocking viral entry into host cells .

Challenges and Considerations