UCLA researchers in the Department of Molecular and Medical Pharmacology have developed a versatile antibody-drug conjugate platform utilizing a novel monoclonal antibody that is highly specific at targeting cancer cells and rapidly internalized by those cells for an effective anti-tumor response.
BACKGROUND:
For decades, an absolute majority of cancer treatments have focused on targeting malignant cells without consideration of the tumor microenvironment (TME) and its unique role in tumor maintenance and progression. Stromal cells in TME actively orchestrate resistance to cancer therapeutics through a myriad of processes such as immune cell regulation, metabolic reprogramming and hypoxia. Aggressive malignancies such as pancreatic adenocarcinoma, glioblastoma multiforme and osteosarcoma rely on the TME for tumor growth and maintenance. The TME differs from normal tissue environments in many aspects, including levels of certain proteins or small molecules. Thus, utilizing the tumor stroma for tumor-specific biomarker discovery could lead to the development of much needed antibodies that can be utilized in antibody-drug conjugates with therapeutic agents for targeted cancer treatment.
INNOVATION:
Researchers led by Dr. Hans David Ulmert in the Department of Molecular and Medical Pharmacology have developed a novel antibody targeting a TME-specific biomarker that is compatible with antibody-drug conjugates. They validated in vitro that the antibody has high binding affinity to various different cancer cell types with few off-target effects. The researchers confirmed that the antibody maintains this high picomolar affinity even when conjugated to adjuvants and is rapidly internalized by cells. The antibody-drug conjugates elicited strong anti-tumor responses in in vivo tumor models.
POTENTIAL APPLICATIONS:
ADVANTAGES:
DEVELOPMENT-TO-DATE:
The study has been validated in vivo.