CM3 Antibody

Introduction to CM3 Antibodies

• CM313: A humanized monoclonal antibody (mAb) targeting CD38, a cell surface protein overexpressed in hematologic malignancies. It exhibits potent cytotoxic activity via antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis induction .

• CM3.B6: A human monoclonal antibody isolated from a chronic HCV patient, targeting a conformational epitope within the NS3 protein of HCV. It recognizes an immunodominant region critical for diagnostic and therapeutic applications .

CM313

• Origin: Generated via hybridoma technology in BALB/c mice immunized with recombinant CD38 protein. Humanization involved computer-assisted optimization of complementarity-determining regions (CDRs) .

• Binding Affinity:

  Target Species	EC₅₀ (nM)
  Human	0.17
  Chimpanzee	0.13
  Source: Flow cytometry and ELISA data

CM3.B6

• Epitope Specificity: Binds a 92-amino-acid sequence (residues 1363–1454) in the NS3 helicase domain. Recognition is conformation-dependent, with minimal binding to linear peptides .

CM313

• Fc-Dependent Cytotoxicity:

  • ADCC: Engages NK cells via FcγRIIIa receptors.

  • CDC: Superior CDC activity compared to isatuximab (EC₅₀: 0.29–0.72 nM vs. 2.43 nM for daratumumab) .

  • Apoptosis: Induces caspase-3/7 activation in CD38⁺ cells .

• Enzymatic Inhibition: Blocks CD38’s ADP-ribosyl cyclase activity, disrupting tumor microenvironment signaling .

CM3.B6

• Diagnostic Utility: Discriminates between viremic and non-viremic HCV patients by targeting an immunodominant NS3 epitope .

CM313

• In Vitro Efficacy:

  • Achieved >90% lysis of CD38⁺ Ramos cells at 10 μg/mL .

  • Reduced soluble CD38 levels in myeloma models by 50% .

• In Vivo Activity:

  • Suppressed tumor growth in xenograft models by 70% (3 mg/kg dose) .

• Safety: No cytokine release or off-target binding observed in human blood cells .

CM3.B6

• Clinical Correlation: Detected in 89% of HCV-infected sera, with high specificity for active infection .

Comparative Analysis

Future Directions

• CM313: Advancing to Phase I trials for CD38⁺ malignancies, with focus on combination therapies .

• CM3.B6: Potential as a biomarker for HCV treatment response monitoring .