Tumor Targeting Peptides for Cytotoxic Chemotherapy Delivery
Annual summary rept. 1 Jul 1998-30 Jun 2001
BURNHAM INST LA JOLLA CA
Pagination or Media Count:
Tumors cannot grow without a blood supply. The distinct characteristics of tumor vasculature make it possible to design therapeutic agents that specifically target the tumor, but not normal blood vessels. Identifying tools for therapeutic tumor targeting was the focus of the project. A new tumor-homing phage F3 was isolated by combining ex vivo screening of a phage cDNA library on cell suspensions prepared from bone marrow and in vivo screening for tumor homing. The F3 phage recognizes the blood vessels in the MDA-MB-435 breast cancers and HL-60 leukemia xenograft tumors. Fluorescein-labeled F3, injected intravenously into mice, accumulates in the endothelium of tumor blood vessels. Small subpopulations of cells in the skin, gut, and bone marrow also pick up F3, but the vessels in normal tissues are all negative. F3 may be a marker of certain progenitor cells. Importantly, the F3 peptide can carry a payload, such as the fluorescein label, into the nucleus of the target cells. It may be particularly well suited as a carrier of drugs that act in the nucleus.
- Medicine and Medical Research