Novel L1CAM-antibody drug conjugates exert potent anti-tumor activity in preclinical models of even advanced pancreatic cancer - PubMed
5 hours ago
- #Pancreatic Cancer
- #Immunotherapy
- #Antibody Drug Conjugate
- Novel L1CAM-antibody drug conjugates (ADCs) show strong anti-tumor activity in preclinical models of advanced pancreatic cancer.
- L1CAM is upregulated in pancreatic ductal adenocarcinoma (PDAC) and contributes to tumor progression and therapy resistance.
- Two L1CAM-ADCs with different toxins (MMAE and SG3199) reduced tumor cell growth by up to 60% in 2D PDAC models.
- Therapeutic efficacy was highest when at least 50% of PDAC cells expressed L1CAM.
- In 3D spheroids, MMAE-conjugated L1CAM-ADC remained effective, while SG3199-conjugated ADC showed reduced efficacy.
- Co-culture with pancreatic myofibroblasts did not impair ADC effects, but macrophages enhanced anti-tumor responses.
- In mouse models, adjuvantly applied MMAE-conjugated L1CAM-ADC reduced pancreatic relapses and peritoneal metastases.
- SG3199-conjugated L1CAM-ADC less impacted pancreatic relapses but nearly eliminated liver and peritoneal metastases.
- Palliative treatment with both ADCs reduced the number and size of liver and peritoneal metastases.
- L1CAM-ADCs demonstrate potential as an immunotherapeutic approach for advanced PDAC.