Abraham Lopez, a senior neuroscience major at Case Western Reserve University, label cancer cells with biotin to facilitate targeted anticancer therapies.
Targeted anticancer therapies have the potential to more effectively attack cancer cells with reduced toxicity, but they are limited by the similarity in surface marker expression between cancer cells and healthy cells. I had very high expectations of the BRSP, but it exceeded my expectations in every way possible. The mentorship I received helped me grow both as a person and as a scientist. The BSRP staff takes very seriously the job of supporting future scientists in every way possible, and they made sure to provide us with as many skills for us to continue succeeding in our career paths. As I look back on nine weeks ago, I can’t believe how much I have grown. I feel a lot more confident as a college student, scientist, and a future doctor. The BSRP 2022 cohort was truly exceptional, and I am very grateful to have spent these past nine weeks with very bright, kind, and wonderful people.Most cancer biomarkers are also expressed to some extent in healthy cells, which can cause side effects such as rash, cardiac dysfunction, thyroid dysfunction, hypertension, and others. One distinguishing feature of tumors is that the tumor microenvironment (TME) has elevated levels of extracellular ATP (~1000-fold compared to healthy tissue). We aim to take advantage of this by using ATP-dependent enzymes to facilitate cancer cell targeting. Biotin ligases (when modified to eliminate substrate specificity) use a molecule of ATP to attach a biotin molecule to nearby proteins. We attached a nanobody against a cancer cell biomarker, CD47, to an optimized biotin ligase so that upon binding, it biotinylates the surface of the target cell. This construct successfully biotinylated melanoma cells (B16) in vitro on a relatively short timescale (1-2 hours) at concentrations as low as 1 nM and was active at TME- relevant ATP concentration (50-200 µM). These proof-of-concept studies demonstrate the feasibility of using a biotin ligase attached to a nanobody or similar ligand to target tumor cells.
Project: Using ATP-dependent Enzyme to Label the Surface of Cancer Cells in Tumors
Mentor: Dr. Rebecca Holden, Cell Circuits