Development and applications of surface-linked single chain antibodies against T-cell antigens

Matthew D. Griffin, Philmore O. Holman, Qizhi Tang, Neda Ashourian, Ulf Korthäuer, David M Kranz, Jeffrey A. Bluestone

Research output: Contribution to journalArticle

Abstract

In this report the use of surface-linkage to expand the potential experimental and therapeutic applications of single chain antibody (scFv) constructs is reviewed. A strategy for the generation and functional characterization of surface-linked scFvs that bind selectively to the T-cell proteins CD3ε, CD28, and CD152 (CTLA-4) is described in detail. Experimental examples are provided of the use of these constructs to study the positive and negative regulation of T-cell activation and to manipulate the in vivo immunogenicity of tumor cells. In addition, a novel system for Simultaneous T-cell Activation and Retroviral Transduction (START) is described in which retroviral packaging cells are rendered mitogenic for T lymphocytes by combined expression of surface-linked scFvs. Finally, the use of random mutagenesis and yeast surface display to increase the affinity and functional efficacy of scFv constructs is demonstrated.

Original languageEnglish (US)
Pages (from-to)77-90
Number of pages14
JournalJournal of Immunological Methods
Volume248
Issue number1-2
DOIs
StatePublished - Feb 1 2001

Fingerprint

Single-Chain Antibodies
Viral Tumor Antigens
T-Lymphocytes
Product Packaging
Mutagenesis
Yeasts
Neoplasms
Proteins
Therapeutics

Keywords

  • CD152
  • CD28
  • CD3
  • Co-stimulation
  • Immunological tolerance
  • Immunomodulation
  • Monoclonal antibodies
  • Neoplasia
  • Protein engineering
  • Retroviral gene transfer
  • T-cell
  • Transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Development and applications of surface-linked single chain antibodies against T-cell antigens. / Griffin, Matthew D.; Holman, Philmore O.; Tang, Qizhi; Ashourian, Neda; Korthäuer, Ulf; Kranz, David M; Bluestone, Jeffrey A.

In: Journal of Immunological Methods, Vol. 248, No. 1-2, 01.02.2001, p. 77-90.

Research output: Contribution to journalArticle

Griffin, Matthew D. ; Holman, Philmore O. ; Tang, Qizhi ; Ashourian, Neda ; Korthäuer, Ulf ; Kranz, David M ; Bluestone, Jeffrey A. / Development and applications of surface-linked single chain antibodies against T-cell antigens. In: Journal of Immunological Methods. 2001 ; Vol. 248, No. 1-2. pp. 77-90.
@article{1bd0e1501ca248cc9d28a7d9af6036a0,
title = "Development and applications of surface-linked single chain antibodies against T-cell antigens",
abstract = "In this report the use of surface-linkage to expand the potential experimental and therapeutic applications of single chain antibody (scFv) constructs is reviewed. A strategy for the generation and functional characterization of surface-linked scFvs that bind selectively to the T-cell proteins CD3ε, CD28, and CD152 (CTLA-4) is described in detail. Experimental examples are provided of the use of these constructs to study the positive and negative regulation of T-cell activation and to manipulate the in vivo immunogenicity of tumor cells. In addition, a novel system for Simultaneous T-cell Activation and Retroviral Transduction (START) is described in which retroviral packaging cells are rendered mitogenic for T lymphocytes by combined expression of surface-linked scFvs. Finally, the use of random mutagenesis and yeast surface display to increase the affinity and functional efficacy of scFv constructs is demonstrated.",
keywords = "CD152, CD28, CD3, Co-stimulation, Immunological tolerance, Immunomodulation, Monoclonal antibodies, Neoplasia, Protein engineering, Retroviral gene transfer, T-cell, Transplantation",
author = "Griffin, {Matthew D.} and Holman, {Philmore O.} and Qizhi Tang and Neda Ashourian and Ulf Korth{\"a}uer and Kranz, {David M} and Bluestone, {Jeffrey A.}",
year = "2001",
month = "2",
day = "1",
doi = "10.1016/S0022-1759(00)00344-6",
language = "English (US)",
volume = "248",
pages = "77--90",
journal = "Journal of Immunological Methods",
issn = "0022-1759",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Development and applications of surface-linked single chain antibodies against T-cell antigens

AU - Griffin, Matthew D.

AU - Holman, Philmore O.

AU - Tang, Qizhi

AU - Ashourian, Neda

AU - Korthäuer, Ulf

AU - Kranz, David M

AU - Bluestone, Jeffrey A.

PY - 2001/2/1

Y1 - 2001/2/1

N2 - In this report the use of surface-linkage to expand the potential experimental and therapeutic applications of single chain antibody (scFv) constructs is reviewed. A strategy for the generation and functional characterization of surface-linked scFvs that bind selectively to the T-cell proteins CD3ε, CD28, and CD152 (CTLA-4) is described in detail. Experimental examples are provided of the use of these constructs to study the positive and negative regulation of T-cell activation and to manipulate the in vivo immunogenicity of tumor cells. In addition, a novel system for Simultaneous T-cell Activation and Retroviral Transduction (START) is described in which retroviral packaging cells are rendered mitogenic for T lymphocytes by combined expression of surface-linked scFvs. Finally, the use of random mutagenesis and yeast surface display to increase the affinity and functional efficacy of scFv constructs is demonstrated.

AB - In this report the use of surface-linkage to expand the potential experimental and therapeutic applications of single chain antibody (scFv) constructs is reviewed. A strategy for the generation and functional characterization of surface-linked scFvs that bind selectively to the T-cell proteins CD3ε, CD28, and CD152 (CTLA-4) is described in detail. Experimental examples are provided of the use of these constructs to study the positive and negative regulation of T-cell activation and to manipulate the in vivo immunogenicity of tumor cells. In addition, a novel system for Simultaneous T-cell Activation and Retroviral Transduction (START) is described in which retroviral packaging cells are rendered mitogenic for T lymphocytes by combined expression of surface-linked scFvs. Finally, the use of random mutagenesis and yeast surface display to increase the affinity and functional efficacy of scFv constructs is demonstrated.

KW - CD152

KW - CD28

KW - CD3

KW - Co-stimulation

KW - Immunological tolerance

KW - Immunomodulation

KW - Monoclonal antibodies

KW - Neoplasia

KW - Protein engineering

KW - Retroviral gene transfer

KW - T-cell

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=0035251546&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035251546&partnerID=8YFLogxK

U2 - 10.1016/S0022-1759(00)00344-6

DO - 10.1016/S0022-1759(00)00344-6

M3 - Article

C2 - 11223070

AN - SCOPUS:0035251546

VL - 248

SP - 77

EP - 90

JO - Journal of Immunological Methods

JF - Journal of Immunological Methods

SN - 0022-1759

IS - 1-2

ER -