Conversion of a tumor-binding peptide identified by phage display to a functional chimeric T cell antigen receptor View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-01

AUTHORS

C R J Pameijer, A Navanjo, B Meechoovet, J R Wagner, B Aguilar, C L Wright, W-C Chang, C E Brown, M C Jensen

ABSTRACT

Adoptive transfer of ex vivo expanded tumor-specific T cells is a promising therapeutic modality for promoting or augmenting antitumor immunity. Several groups, including ours, are developing antigen receptor gene transfer strategies as a means of generating effector cells for adoptive therapy. Chimeric antigen receptors (CARs) have been described that use single-chain antibodies or cytokine ligands as tumor targeting domains. Here, we describe the capacity of a tumor-binding peptide identified by phage display combinatorial library screening to serve as a CAR targeting domain. A phage library-selected high-affinity 12-mer peptide (Bpep) specific for alpha(v) beta(6) integrin (alpha v beta6) was chosen for these studies. Primary human T cells were genetically modified to express the Bpep-CAR consisting of an alpha v beta6-specific peptide and human IgG4 hinge-Fc extracellular domain fused to the cytoplasmic tail of CD3-zeta. T cell expression of the Bpep-CAR was assessed by Western blot analysis, and trafficking of the Bpep-CAR to the cell surface was demonstrated by flow cytometry. Functionally, Bpep-CAR redirected cytotoxic T lymphocytes specifically kill integrin alpha v beta6+ ovarian tumor targets, and are activated for interferon gamma secretion. Our data suggest that large new repertoires of tumor-specific T cell antigen receptor transgenes might be available through merging combinatorial peptide libraries with CAR construct design. More... »

PAGES

7700993

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.cgt.7700993

DOI

http://dx.doi.org/10.1038/sj.cgt.7700993

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1026932809

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17024231


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