The long term goal of this project is the development of synthetic peptide-based therapy for Human B-cell lymphomas. The phase I period will serve (1) to test the feasibility of identifying peptide ligands of the surface immunoglobulin antigen receptors (IgR) from patients' tumors; and (2) to test the in vivo efficacy of synthetic peptide ligands in the SUP- B8 SCID mouse model system. The specific tasks to be accomplished are: 1) Isolate the soluble IgR from culture supernatant of hybridomas previously established from patient lymphoma biopsies. 2) Screen a variety of random peptide libraries against each immunoglobulin preparation to find specific peptide ligands. (The libraries contain peptides 8 to 20 residues in length expressed on the pIII and pVIII coat proteins of filamentous phage, or fused to Laci complexed with plasmids, or displayed as nascent peptides in polysomes.) 3) Synthesize, purify, and confirm the sequence of the peptide ligands. 4) Characterize the specificities, affinities, and biological activities of these peptides. 5) Test the efficacy of the synthetic peptides in SCID mouse model by treating mice bearing the human tumor with a series of peptide administration protocols.
The tumor-specific cytotoxic activity of the peptide ligands identified to date provides an opportunity for rapidly creating customized therapeutic reagents specific for the tumors of B-cell lymphoma patients. Such specific therapeutic reagents might be used alone, a protocol with low potential for deleterious side effects, or in combination with less specific tumor ablation therapies including conventional chemotherapy and radiation.
| Renschler, M F; Dower, W J; Levy, R (1998) Identification of peptide ligands for the antigen binding receptor expressed on human B-cell lymphomas. Methods Mol Biol 87:209-34 |
