Generation of MANAbodies specific to HLA-restricted epitopes encoded by somatically mutated genes.

ABSTRACT: Mutant epitopes encoded by cancer genes are virtually always located in the interior of cells, making them invisible to conventional antibodies. We here describe an approach to identify single-chain variable fragments (scFvs) specific for mutant peptides presented on the cell surface by HLA molecules. We demonstrate that these scFvs can be successfully converted to full-length antibodies, termed MANAbodies, targeting "Mutation-Associated Neo-Antigens" bound to HLA. A phage display library representing a highly diverse array of single-chain variable fragment sequences was first designed and constructed. A competitive selection protocol was then used to identify clones specific for mutant peptides bound to predefined HLA types. In this way, we obtained two scFvs, one specific for a peptide e

SUBMITTER: Skora AD 

PROVIDER: S-EPMC4538619 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature