The carbohydrate antigen sialyl-Lewis a (sLea), also known as CA19.9, is widely expressed in pancreatic cancer (PC), and serum CA19.9 expression is used as a tumor marker in PC. sLea serves as a ligand for E-selectin adhesion molecules and over-expression of sLea may be a key event in invasion and metastasis. We have generated a series of fully human monoclonal antibodies (mAb) and 5B1 (IgG1/λ) was selected for further studies based on high affinity and exquisite specificity for sLea. Remarkable in vivo efficacy was demonstrated with a series of pancreatic and other cancer cell lines in SCID mice. Radiolabeled 5B1 (89Zr-5B1) was demonstrated to specifically localize tumors in multiple models, including subcutaneous and orthotopic models of PC, out-performing FDG-PET by imaging these earlier and more clearly, even in the presence of high serum CA19.9 levels.
The specific aims for this proposal are to perform proof of concept preclinical studies and preliminary toxicological studies, and the long-term objective is to evaluate 5B1 utility in a Phase 0/1 clinical study.
