CHEEMA-THESIS-2017.pdf (915.11 kB)
Pancreatic Tumor Cell Capture via Dendrimer-Mediated Multivalent Binding and Antibody Cocktail
thesisposted on 2017-10-27, 00:00 authored by Mehar K Cheema
Pancreatic cancer is one of the most invasive and lethal cancers, due to the associated extremely high mortality rate. Circulating tumor cells (CTCs) are one indicator that can be used to diagnostically measure the progression of pancreatic cancer, the prognostic outcomes, and varying factors including chemotherapy effectiveness. In this study, we aimed to combine G7 poly(amidoamine) (PAMAM) dendrimers and a three antibodies targeted specifically towards pancreatic tumor cells, including cell surface proteins Epithelial Cell Adhesion Molecule (EpCAM), Epidermal Growth Factor Receptor (EGFR), and Carcinoembryonic Antigen (CEA). Through integration of the multivalent binding effect via G7 PAMAM dendrimers and the cocktail of the three antibodies, we designed and engineered a CTC capture system that exhibits a high recovery yield compared to existing CTC detection technologies. Our results demonstrate preliminary findings that the capture surface with G7 dendrimers exhibits a significantly higher recovery yield (60-70%), compared to the surfaces without dendrimers (20-40% recovery yield). Furthermore, our results also show that the triple antibody system of EpCAM/EGFR/CEA exhibits 15-20% greater recovery yield when combined with G7 dendrimers than the surfaces with each of antibodies immobilized individually. These findings provide the preliminary groundwork of developing this CTC detection system to be used for blood samples from pancreatic cancer patients, potentially allowing early and accurate diagnosis through enhanced detection and analysis of pancreatic cancer CTCs. Future work of testing this CTC detection system using a variety of clinical cancer patients will validate the clinical impact of this approach that has potential to supplement current methods, such as solid biopsy, for cancer diagnosis and prognosis.
ChairEddington, David T
Degree GrantorUniversity of Illinois at Chicago