An antibody-drug conjugate designed through clone and isotype selection restricts the growth of CSPG4-expressing triple-negative breast cancer - PubMed
4 days ago
- #CSPG4
- #antibody-drug conjugate
- #triple-negative breast cancer
- Antibody-drug conjugates (ADCs) show promise for treating aggressive triple-negative breast cancers (TNBCs).
- Chondroitin sulfate proteoglycan 4 (CSPG4) was identified as a target in treatment-resistant TNBC.
- Three anti-CSPG4 IgG1 antibodies (225.28S, 763.74, and 9.2.27) were engineered and compared.
- 225.28S IgG1 demonstrated superior internalization and cytotoxicity when conjugated to MMAE.
- 225.28S IgG1 outperformed IgG4 in internalization and killing as an MMAE-conjugated ADC.
- A DXd-conjugated ADC with a drug-to-antibody ratio (DAR) of 8 showed robust internalization and cytotoxicity in vitro.
- The ADC significantly restricted growth in CSPG4-expressing TNBC patient-derived xenografts (PDX).
- Unconjugated 225.28S IgG1 also limited TNBC xenograft growth, confirming Fc-mediated activity.
- 225.28S IgG1 is identified as the optimal clone and isotype for ADC development.
- The study supports DXd-conjugated ADCs as a promising strategy for CSPG4-expressing TNBC.