The
orphan receptor 1 (ROR1) is a cell surface protein found in various blood and
solid tumors, making it a promising therapeutic target for
ROR1-positive
cancers. This research introduces a pioneering anti-ROR1 monoclonal antibody drug conjugate (ADC) named XBR1-402 or its humanized variant, huXBR1-402. These are linked to a potent anthracycline-derived toxin,
PNU-159682 (PNU), and have demonstrated efficacy in eliminating ROR1-positive
chronic lymphocytic leukemia (CLL),
mantle cell lymphoma (MCL), and
pre B cell acute lymphocytic leukemia (pre B cell ALL) cells.
In the study, a reduction in viability was observed in all ROR1-positive leukemic cell lines treated with the ADC. Notably, the ROR1-positive pre B cell ALL cell lines 697 and Kasumi-2 exhibited a marked decrease in viability when treated with XBR1-402-PNU compared to the control
Trastuzumab-PNU. Similarly, the ROR1-positive Jeko and Mino cell lines of MCL showed decreased viability with
huXBR1-402-PNU treatment, while the ROR1-negative Mec-1 cell line remained unaffected.
Although direct cytotoxicity wasn't significant in primary CLL cells, the PNU ADCs were found to mediate antibody-dependent cellular cytotoxicity and phagocytosis. The ADCs also induced a G2/M cell cycle arrest in affected cell lines, suggesting that targeting proliferating cells in lymphoid organs may be a strategy for PNU's therapeutic action.
In vivo studies on a murine 697 ALL model indicated that XBR1-402-PNU treatment significantly increased overall survival compared to the control. Additionally, in vivo CLL studies with huXBR1-402-PNU showed both a reduction in
leukemia burden and an increase in overall survival.
The findings indicate that the anti-ROR1 ADC huXBR1-402-PNU is a potential and effective targeted therapy for ROR1-positive leukemic cells and warrants further exploration for clinical application in ROR1-positive leukemia and lymphomas.
How to Use Synapse Database to Search and Analyze Translational Medicine Data?
The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

Click on the image below to go directly to the Translational Medicine search interface.
