Wagner Lab Research Targets Cancer with CSANs
March 29, 2023
Over the past decades we have learned that cancer is a very complex disease. There are many forms of cancer arising from organ specific malignancies that can further metastasize to other organs. Tumors themselves are now recognized to not just be one type of cell but a community of many different types of cells, including many types of tumor cells. Key among these cells are what are being called cancer stem cell like cells or CSCs. Although generally few in number, evidence is growing that supports the theory that CSCs are key to the progression and growth of a tumor. Because CSCs tend to be resistant to chemotherapy and radiation, even when it appears the cancer has gone into remission, the cancer can re-appear sometimes months or years after treatment.
Over the past few years, Prof. Carston “Rick” Wagner’s Lab has been designing chemically self-assembled nanorings, referred to as CSANs, that can engage and guide the bodies T-cells to seek out and destroy tumor cells. They have applied this strategy to breast cancer, colon cancer and even brain cancers like medulloblastoma. Recently, in a paper published in the journal, Molecular Cancer Therapeutics, and co-authored with medicinal chemistry graduate student, Jake Petersburg and collaborator, Prof. Daniel Vallera (UMN Deptartment of Radiology), the Wagner group reported that bispecific CSANs capable of binding to the T-cell activating protein on T-cells, CD3, and the common tumor antigen EpCam, was able to significantly reduced the growth of triple negative breast cancer in mice, but not cure them. If they then treated the mice with CSANs that able to bind to CD3 and CD133, which is found on CSCs, the tumors stopped growing, but were not eliminated. However, it the mice with TNBC tumors were treated with an equal amount of CSANs targeting CD3 and EpCam and CSANs targeting CD3 and CD133, complete eradication of the tumors was observed, with 80% of the animals being cured. These findings suggest targeting both the primary tumor and CSCs might be required for permanent long term cancer survival.
The Wagner group is now examining other types of TNBCs, as well as other cancer types, to assess the generality of this approach for tumor eradication. The potential for these discoveries to be translated into the clinic is being explored by a start-up company, Tychon Bioscience, Inc., he co-founded with Invenshure, Inc. Support for this research is gratefully acknowledged from the National Cancer Institute, Tychon Bioscience, Inc. and the University of Minnesota Academic Health Center.
Related Article: Petersburg J, Vallera DA, Wagner CR. Eradication of Heterogeneous Tumors by T Cells Targeted with Combination Bispecific Chemically Self-assembled Nanorings. Mol Cancer Ther. 2023 Mar 2;22(3):371-380.