First Clinical Study Targeting ROR1, A Cancer Stem Cell Antigen Involved In Rho-GTPase Activation

Cirmtuzumab is a humanized monoclonal antibody that selectively targets ROR1, which is expressed on cancer stem cells (CSCs). Patients experienced reversal of the stemness gene expression signature associated with oncogenic dedifferentiation, inhibition of leukemia-cell activation of Rho-GTPases and HS1, reductions in leukemia cell counts, and prolonged time-to-next-treatment (TTNT) following only 4 biweekly infusions of cirmtuzumab. Peripheral Blood Mononuclear Cells (PBMC) of 3 CLL samples were collected at day 0 (Pre) and at day 28 of cirmtuzumab treatment (Post). Negative isolation of CLL cells to ≥95% purity was performed prior to RNA isolation. Data were analyzed by Rosalind (https://rosalind.onramp.bio/), with a HyperScale architecture developed by OnRamp BioInformatics, Inc. (San Diego, CA).