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Selection of Chronic Lymphocytic Leukemia Binding Peptides¹

Center for Cell and Gene Therapy [S. T., M. K. B., M. A. B., H. M., M. B. P.] and Departments of Pediatrics [M. K. B.], Molecular and Human Genetics [M. A. B.], and Immunology [M. B. P., M. A. B.], Baylor College of Medicine, Houston, Texas 77030; Department of Bioengineering, Rice University, Houston, Texas 77251 [H. M., M. A. B.]; and Department of Molecular Hematology and Therapy, MD Anderson Cancer Center, Houston, Texas 77030 [F. C. M., M. A.]

To provide cell-binding ligands for ex vivo gene therapy and chronic lymphocytic leukemia (CLL)-targeting ligands for in vivo drug and gene therapy, we selected 44 20-mer peptides from peptide-presenting phage libraries by panning against primary patient CLL cancer cells. Twenty-nine of the selected peptides were assayed for cell binding. Eight of the selected peptides bound CLL cells, B cells, T cells, and monocyte cells, 12 bound only CLL cells and B cells, and 1 peptide bound only B cells. However, eight of the selected peptides were CLL specific. When two of the peptides were tested out of the context of phage, the synthetic peptides were able to bind cells and functionally retarget adenovirus to increase ex vivo gene delivery to primary CLL cells. These data demonstrate the ability to identify lead cancer-targeting peptides by selection of phage libraries against primary human cancers cells.

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