Researchers at University of Pittsburgh have isolated fully human antibodies with the potential to target prostate stem cell antigen (PSCA) as a therapeutic approach for prostate cancer.
Description
SCA is found to be upregulated in various solid tumors, including prostate, bladder, renal cell, and pancreatic cancers. It is thought that PSCA could serve as a potential immunotherapeutic target for prostate cancers due to its positively correlated expression with tumor grade and disease extent. Furthermore, PSCA is remarkably found to be expressed at 100% of bone metastases of prostate cancer. Over the years, several monoclonal antibodies have been identified that target PSCA, but most of these were derived from mouse. Here, researchers have identified fully human antibodies isolated from a highquality phage-displayed antibody Fab library. These antibodies have shown robust ADCC and internalization into PSCA expressing cancer cells, establishing the foundation of generation of antibody-drug conjugates (ADCs) to combat prostate cancer. The antibody-MMAE conjuates erasdicated xenografted prostate tumors in NSG mouse models, without causing overt toxicity. The identified fully human PSCA antibody and ADC thereof bear promising applications against PSCA+ solid tumors.
Applications
Prostate cancer/Pancreatic cancer/Bladder cancer
Advantages
This innovation has unique features, including broad applications to various types of PSCA expressing solid tumors, fullyhuman antibodies with low risk of inducing immunogenicity, effective internalization suitable for ADC, robust ADCC and unique epitopes from central PSCA that can be recognized by the Fab antibody.
Invention Readiness
The work has reached the in vivo development stage.
IP Status
https://patents.google.com/patent/WO2024233662A2