Antibody Conjugation to Carborane Dendrimers for the Treatment of Pancreatic Cancer

Summer 2019

Andrew Hong : Chemistry

Mentor: Robert Flavell

Pancreatic cancer is one of the deadliest cancers nationwide, due to the dearth of effective treatment options. While KRAS oncogenic mutations are ubiquitous in pancreatic cancer, there is no anti-KRAS therapeutic for routine clinical use. One promising alternative may be boron neutron capture therapy (BNCT), which entails the irradiation of internalized boron atoms in cancer cells. In particular, carborane compounds are clinically promising for serving as effective cytotoxic BNCT agents. Therefore, I propose to improve upon current carboranyl molecules to develop a highly boronated dendrimer which will be conjugated to an antibody targeting the CDCP1 protein, which is a biomarker for mutant KRAS. Subsequently, the conjugate will be delivered to in vitro and in vivo pancreatic cancer models and be evaluated on its ability to preferentially deliver boron to pancreatic cancer cells over non-pancreatic cancer cells. Through its efficacy and selectivity, the proposed bioconjugate may ultimately improve patient outcomes for pancreatic cancer.

I am very grateful to the Rose Hills Foundation for providing me with the opportunity to focus on research full-time this upcoming summer. This fellowship will allow me to not only expand my understanding of medicinal chemistry, but also grow as a scientist. Ultimately, this fellowship will be invaluable as I pursue a career as a physician-scientist.