T cell receptor-like recognition of tumor in vivo by synthetic antibody fragment.

A major difficulty in treating cancer is the inability to differentiate between normal and tumor cells. The immune system differentiates tumor from normal cells by T cell receptor (TCR) binding of tumor-associated peptides bound to Major Histocompatibility Complex (pMHC) molecules. The peptides, der...

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Autores principales:	Keith R Miller, Akiko Koide, Brenda Leung, Jonathan Fitzsimmons, Bryan Yoder, Hong Yuan, Michael Jay, Sachdev S Sidhu, Shohei Koide, Edward J Collins
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/63f17489ca874bf196d8e8ddb9f027b5
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spelling	oai:doaj.org-article:63f17489ca874bf196d8e8ddb9f027b52021-11-18T07:08:09ZT cell receptor-like recognition of tumor in vivo by synthetic antibody fragment.1932-620310.1371/journal.pone.0043746https://doaj.org/article/63f17489ca874bf196d8e8ddb9f027b52012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22916301/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203A major difficulty in treating cancer is the inability to differentiate between normal and tumor cells. The immune system differentiates tumor from normal cells by T cell receptor (TCR) binding of tumor-associated peptides bound to Major Histocompatibility Complex (pMHC) molecules. The peptides, derived from the tumor-specific proteins, are presented by MHC proteins, which then serve as cancer markers. The TCR is a difficult protein to use as a recombinant protein because of production issues and has poor affinity for pMHC; therefore, it is not a good choice for use as a tumor identifier outside of the immune system. We constructed a synthetic antibody-fragment (Fab) library in the phage-display format and isolated antibody-fragments that bind pMHC with high affinity and specificity. One Fab, fE75, recognizes our model cancer marker, the Human Epidermal growth factor Receptor 2 (HER2/neu) peptide, E75, bound to the MHC called Human Leukocyte Antigen-A2 (HLA-A2), with nanomolar affinity. The fE75 bound selectively to E75/HLA-A2 positive cancer cell lines in vitro. The fE75 Fab conjugated with (64)Cu selectively accumulated in E75/HLA-A2 positive tumors and not in E75/HLA-A2 negative tumors in an HLA-A2 transgenic mouse as probed using positron emission tomography/computed tomography (PET/CT) imaging. Considering that hundreds to thousands of different peptides bound to HLA-A2 are present on the surface of each cell, the fact that fE75 arrives at the tumor at all shows extraordinary specificity. These antibody fragments have great potential for diagnosis and targeted drug delivery in cancer.Keith R MillerAkiko KoideBrenda LeungJonathan FitzsimmonsBryan YoderHong YuanMichael JaySachdev S SidhuShohei KoideEdward J CollinsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e43746 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Keith R Miller Akiko Koide Brenda Leung Jonathan Fitzsimmons Bryan Yoder Hong Yuan Michael Jay Sachdev S Sidhu Shohei Koide Edward J Collins T cell receptor-like recognition of tumor in vivo by synthetic antibody fragment.
description	A major difficulty in treating cancer is the inability to differentiate between normal and tumor cells. The immune system differentiates tumor from normal cells by T cell receptor (TCR) binding of tumor-associated peptides bound to Major Histocompatibility Complex (pMHC) molecules. The peptides, derived from the tumor-specific proteins, are presented by MHC proteins, which then serve as cancer markers. The TCR is a difficult protein to use as a recombinant protein because of production issues and has poor affinity for pMHC; therefore, it is not a good choice for use as a tumor identifier outside of the immune system. We constructed a synthetic antibody-fragment (Fab) library in the phage-display format and isolated antibody-fragments that bind pMHC with high affinity and specificity. One Fab, fE75, recognizes our model cancer marker, the Human Epidermal growth factor Receptor 2 (HER2/neu) peptide, E75, bound to the MHC called Human Leukocyte Antigen-A2 (HLA-A2), with nanomolar affinity. The fE75 bound selectively to E75/HLA-A2 positive cancer cell lines in vitro. The fE75 Fab conjugated with (64)Cu selectively accumulated in E75/HLA-A2 positive tumors and not in E75/HLA-A2 negative tumors in an HLA-A2 transgenic mouse as probed using positron emission tomography/computed tomography (PET/CT) imaging. Considering that hundreds to thousands of different peptides bound to HLA-A2 are present on the surface of each cell, the fact that fE75 arrives at the tumor at all shows extraordinary specificity. These antibody fragments have great potential for diagnosis and targeted drug delivery in cancer.
format	article
author	Keith R Miller Akiko Koide Brenda Leung Jonathan Fitzsimmons Bryan Yoder Hong Yuan Michael Jay Sachdev S Sidhu Shohei Koide Edward J Collins
author_facet	Keith R Miller Akiko Koide Brenda Leung Jonathan Fitzsimmons Bryan Yoder Hong Yuan Michael Jay Sachdev S Sidhu Shohei Koide Edward J Collins
author_sort	Keith R Miller
title	T cell receptor-like recognition of tumor in vivo by synthetic antibody fragment.
title_short	T cell receptor-like recognition of tumor in vivo by synthetic antibody fragment.
title_full	T cell receptor-like recognition of tumor in vivo by synthetic antibody fragment.
title_fullStr	T cell receptor-like recognition of tumor in vivo by synthetic antibody fragment.
title_full_unstemmed	T cell receptor-like recognition of tumor in vivo by synthetic antibody fragment.
title_sort	t cell receptor-like recognition of tumor in vivo by synthetic antibody fragment.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/63f17489ca874bf196d8e8ddb9f027b5
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T cell receptor-like recognition of tumor in vivo by synthetic antibody fragment.

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