Feng Lin, PhD | Daniel Lindner, MD, PhD | Brian Hill, MD, PhD

Lerner Research Institute | Taussig Cancer Institute

LYMPHOMA

Pilot Award

Potential of a CD6-Targeted Antibody-Drug Conjugate as a Novel Therapy for Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma with poor clinical prognosis and no cure. Currently available management options are limited and with severe side effects. Furthermore, most MCL patients relapse and become refractory to these treatments. In pilot studies examining MCL patient specimens, we found evidence suggesting that CD6, a surface protein primarily expressed on T cells and a small fraction of B cells called B1 cells, as a new therapeutic target for MCL. We thus developed a novel CD6-targeted antibody-drug conjugate (ADC) with a FDA-approved mitotic toxin as the payload, which is designed to selectively kill the actively proliferating MCL tumor cells while sparing the normal cells despite their expression of CD6. In this application, we will first demonstrate that this ADC selectively kills proliferating MCL cells while sparing normal B cells as well as other CD6+ cells such as normal T cells in vitro, then determine its in vivo treatment efficacy and potential adverse effects in a preclinical models of MCL. These studies will provide the required proof-of-concept for future federal grant applications towards further clinical development of this ADC as a novel drug for treating patients with MCL.

IN OTHER WORDS

Our study is focused on how an anti-body drug can target cancer cells. The anti-bodies in the drug help it attack lymphoma cells. We want to come up with a therapy using this drug that is specific to killing tumor cells and helps to minimize side effects of killing healthy cancer cells.