Generation of antibody-based therapeutics targeting the Idiotype of B-cell Malignancies.

ABSTRACT:

Background

A feature of many B-cell tumors is a surface-expressed immunoglobulin (sIg). The complementarity determiningregions (CDRs)of the sIg, termed the 'idiotype', are unique to each tumor. We report on a phage selection strategy to generate anti-idiotype therapeutics that react with sIg CDR3 sequences: the MEC1 B-cell tumor line was used as proof of concept.

Methods

To create a mimetic of the MEC1 idiotype, CDR3 sequences from heavy and light chains of the sIg were grafted into a scFv framework scaffold. Using the Tomlinson I phage library of human scFvs, we enriched for binders to MEC1 CDR3 sequences over unrelated CDR3 sequences.

Results

By ELISA we identified 10 binder phage. Of these, five were sequenced, found to be unique and characterized further. By flow

SUBMITTER: Weiss E 

PROVIDER: S-EPMC6383771 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature