Tumor Targeting Peptides for Cytotoxic Chemotherapy
Abstract
The current high dose chemotherapy for leukemia and other hematological malignancies is very toxic and therefore therapeutic targeting would be particularly useful. Phage display of random peptides or short proteins has been used in vivo to identify tissue specific endothelial address molecules. Coupling of these homing molecules to cytotoxic drugs or therapeutic cells has resulted in targeted therapies with a low toxicity and a good efficacy profile. We have recently characterized several bone marrow (BM) and tumor targeting peptides/proteins from phage libraries displaying 6-10 random amino acids or cDNA molecules, and by utilizing a combination of ex vivo and in vivo phage display. The main purpose of this project is to develop an efficient cancer therapy targeted to BM. As a first step, we are currently constructing drug molecules where a BM targeting peptide is coupled to nucleoside antimetabolites in order to decrease dose or usage limiting non-BM toxicity. These constructs will be tested for therapeutic and targeting efficacy on leukemic cells and in mice leukemia models.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA387098
Entities
People
- Kimmo Porkka
Organizations
- Sanford Burnham Prebys Medical Discovery Institute