Identification of Novel Peptide Ligands Targeting α4β1 Integrins on Patient Lymphoma Cells

Abstract 4854

Peptides are promising cancer-targeting agents—they are small, chemically stable, easy to synthesize and can be readily conjugated to toxins, radionucleotides, or drugs. The “one-bead one-compound” (OBOC) combinatorial libraries developed in the Lam lab consist of millions of beads, each displaying one unique peptide entity. Through high throughput screening peptide combinatorial libraries against cancer cell lines, peptides can be selected and engineered to recognize some certain receptors on the cell surface. From our previous screen, we observed that the LLP2A peptide sequence bound to the α4β1 integrin on the cell surface of a variety of malignant lymphoid cell lines. We hypothesize that more specific ligands against the α4β1 integrin on human patient lymphoma cells could be identified through screening focused LLP2A libraries. Two OBOC-focused combinatorial libraries based on the LLP2A peptide sequence were designed, synthesized and screened against human patient lymphoma cells to search for ligands with higher binding affinity. We selected the candidate peptide sequences that displayed a higher strength for the patient lymphoma cells using the whole cell binding assay, an in vitro approach for quantitating the strength of peptide interaction with cell surface molecules on the cancer cells. We are currently analyzing the data to determine the specific sequence requirements for higher affinity binding. Further assessment of the affinity and kinetics of integrin-peptide binding will be performed using flow cytometry.