Johns Hopkins University

Andrew Josef Ewald

Antony Rosen

Livia Angela Casciola-Rosen

Kevin Cheung

Veena Padmanaban

The present disclosure provides, among other things, compositions (e.g., autoantibodies) that inhibit the growth, viability, or mobility of (invasion by) a cancer cell. Also provided are applications, such as therapeutic and diagnostic methods, in which the agents are useful, as well as screening methods for identifying autoantibodies useful in the applications.

Autoimmune antibodies for use in inhibiting cancer cell growth

Carcinomas typically invade as a cohesive multicellular unit, a process termed collective invasion. It remains unclear how different subpopulations of cancer cells contribute to this process. We developed three-dimensional (3D) organoid assays to identify the most invasive cancer cells in primary breast tumors. Collective invasion was led by specialized cancer cells that were defined by their expression of basal epithelial genes, such as cytokeratin-14 (K14) and p63. Furthermore, K14+ cells led collective invasion in the major human breast cancer subtypes. Importantly, lumenal cancer cells were observed to convert phenotypically to invasive leaders following induction of basal epithelial genes. Although only a minority of cells within lumenal tumors expressed basal epithelial genes, knockdown of either K14 or p63 was sufficient to block collective invasion. Our data reveal that heterotypic interactions between epithelial subpopulations are critical to collective invasion. We suggest that targeting the basal invasive program could limit metastatic progression.

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Catonsville, MD, United States of America

Andrew Josef Ewald