New Method of Treating B-Cell Cancers

Case ID:
16-1331

Background Non-Hodgkin’s Lymphomas (NHL) is one of the most frequent malignant lymphomas found in both children and adults with over 70,000 cases a year in the US. B-cell lymphomas make up nearly 85% of NHL cases. The most common type of treatment is an aggressive form of chemotherapy with or without the addition of newer antibody based drug called rituximab. However, these intensive treatments are often associated with significant side effects and there are over 20,000 deaths a year in the US from NHL making it an important area of research for developing new therapies.

Researchers at WSU have been studying an enzyme Activation-Induced Deaminase (AID) and its role in normal B cell maturation and B cell cancer development.  It is known AID converts DNA cytosines to uracils in immunoglobulin genes, creating antibody diversification however this also leads to the creation of absaic sites which can result in mutations and translocations that promote cancer.  By developing tools to quantify abasic sites and genomic uracil then studying numerous cell lines they discovered a clear correlation between high AID expression levels and certain GC-derived B cell cancers.

Technology Summary:  WSU researchers have discovered a new method of treating B cell cancers which selectively kills only cells lines over-expressing AID.  Extensive in vitro work on numerous cell lines compared the method of selective killing B-cell lines such as Daudi, Ramos1, Raji, Toledo and patient B-cell lines to the effect on non-B cell cancers and healthy cells such as MCF7, MDA-MB 453, Hela, HEK293, A459, mouse splenocytes, Human B cells and Human T cells. For cells lines that do not over express AID, the method was non-toxic up to 20 mM while showing 20x selectivity for B cell lines. WSU researchers are continuing to work on optimizing the treatment method but have shown promising results compared to clinical trial compounds that target similar binding sites.

Highlights

·         Demonstrated selective killing of B Cell lymphomas

·         Novel anticancer chemotherapy specific for hematological cancers

References
2014 “Genomic Uracil Homeostasis during Normal B Cell Maturation and Loss of This Balance during B Cell Cancer Development” MOLECULAR AND CELLULAR BIOLOGY 34 (21) pp 4019-4032

2015 “A versatile new tool to quantify abasic sites in DNA and inhibit base excision repair” DNA REPAIR 27 pp9-18

Patent Information:
For Information, Contact:
Nicole Grynaviski
Commercialization Principal
Wayne State University
nicole.grynaviski@wayne.edu
Inventors:
Ashok Bhagwat
Keywords: