T Cell Receptor-Like Recognition of Tumor In Vivo by Synthetic Antibody Fragment

• DOI: 10.1371/journal.pone.0043746
• Publication Date: 2012-08-20T21:14:09Z
• Authors: Keith R. Miller; Akiko Koide; Brenda Leung; Jonathan Fitzsimmons; Bryan Yoder; Hong Yuan; Michael Jay; Sachdev S. Sidhu; Shohei Koide; Edward J. Collins
• Keywords: Cancer Immunotherapy

A major difficulty in treating cancer is the inability to differentiate between normal and tumor cells. The immune system differentiates from cells by T cell receptor (TCR) binding of tumor-associated peptides bound Major Histocompatibility Complex (pMHC) molecules. peptides, derived tumor-specific proteins, are presented MHC which then serve as markers. TCR a difficult protein use recombinant because production issues has poor affinity for pMHC; therefore, it not good choice identifier outside system. We constructed synthetic antibody-fragment (Fab) library phage-display format isolated antibody-fragments that bind pMHC with high specificity. One Fab, fE75, recognizes our model marker, Human Epidermal growth factor Receptor 2 (HER2/neu) peptide, E75, called Leukocyte Antigen-A2 (HLA-A2), nanomolar affinity. fE75 selectively E75/HLA-A2 positive lines vitro. Fab conjugated (64)Cu accumulated tumors negative an HLA-A2 transgenic mouse probed using positron emission tomography/computed tomography (PET/CT) imaging. Considering hundreds thousands different present on surface each cell, fact arrives at all shows extraordinary These antibody fragments have great potential diagnosis targeted drug delivery cancer.