Lymphomas and leukemias accounted for 96,000 newly diagnosed cancer cases in the United States in 2004. These cancers resulted in an estimated 44,000 deaths, or approximately 8% of all cancer related deaths, in the same year. Targeted therapy for subtypes of B cell malignancy with anti-CD20 antibody (rituxin, rituximab) has shown promise in slowing the progress of disease but a complete cure is observed in less than 10 percent of the patients.
Unfortunately, anti-CD20 antibody therapy is not effective for over 50 percent of the newly diagnosed Non-Hodgkin’s lymphoma (NHL) patients. An additional complication to the use of anti-CD20 antibody is that this marker is expressed at significant levels on the normal mature B cell population. Depending on the form of therapy, these normal cells will be targeted along with the tumor cells. Thus, there is still a need for new ligands to target malignancies of bone marrow origin as well as other sites in the body while sparing normal tissues.
Towards this goal, we have recently applied biopanning to the A20 cell line, a murine B cell lymphoma line. Three ligands that discriminate malignant and normal lymphocytes were selected from a phage displayed peptide library. Importantly, these phage bind to other bone marrow derived cancer cell lines including some macrophage and T cells but do not bind to normal splenocytes. The synthetic peptides have binding affinities comparable to B cell specific antibodies and can be used to distinguish lymphoma cells from normal splenocytes by flow cytometry and magnetic bead capture. Current focus of this research involves:
- Testing these peptides for binding to primary human lymphomas and normal B cells
- Expanding the number of cell specific reagents for human lymphomas
- Utilizing the ligand for the development of new clinical diagnostic reagents
- Establishing targeted delivery in animal models
More information can be found in the following publication:
- McGuire, Michael J.; Samli, Kausar N.; Chang Ya-Ching; Brown Kathlynn C. (2006) “Novel Ligands for Cancer Diagnosis: Selection of Peptide Ligands for Identification and Isolation of B-Cell Lymphomas”. Experimental Hematology; 34, 443-452