In Vivo Selection of Ligands for Targeted Therapy

University Of Vermont &St Agric College, Burlington VT

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Using phage-displayed random peptide libraries, our goal is to develop tumor-targeting ligands for cancer therapy. The approach is administer the phage library intravenously, surgically sample tumor tissue, and collect phage which has bound to the tumor. Preclinical cytotoxicity testing has been performed and the FDA has issued an IND to proceed with human studies. The rationale for this approach is based on published experiments in animals that resulted in identification of ligands to vascular targets that appear tumor specific and our own preclinical feasibility testing in animal models demonstrating a good safety profile. The benefits of performing this procedure in human cancer patients include the presence of a vast number of possible targets which are otherwise not available in vitro, targets will be in their native configuration, subtraction of the pools of ligands binding to normal tissue, identification of peptide ligands which will be stable in blood, the possibility of identifying unique targets for an individual patient, and the rapidity of the process. Hypotheses: 1) Serial administration of a phage-displayed random peptide library (RPL) is nontoxic to cancer patients. 2) Phage collected from tumor deposits in patients following systemic administration of RPL will containtumor selective peptide ligands. The Specific Aims are 1) Intravenously administer a naive RPL library to cancer patients, surgically harvest phage-bearing tumor nodule, and collect phage from tumor sample. This process will be repeated twice with infusion of phage that bound to tumor. 2) Establish safety of serial systemic administration of naive and enriched RPL collected from patient tumor deposits. 3) Determine peptide sequences of phage collected from harvested tumor specimens. 4) Determine whether candidate clones bind selectively to tumor tissue specimens. Successful completion of this clinical study will result in demonstration of a satisfactory safety profile and short peptides that bind selectively to tumor tissue.