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

doi:10.1016/S0022-1759(00)00344-6

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

Biochemistry

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Pages (from-to)	77-90
Number of pages	14
Journal	Journal of Immunological Methods
Volume	248
Issue number	1-2
DOIs	https://doi.org/10.1016/S0022-1759(00)00344-6
State	Published - Feb 1 2001

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

Online availability

10.1016/S0022-1759(00)00344-6

Library availability

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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.}",

note = "Funding Information: This work was supported by a grant from the Roche Organ Transplant Research Foundation (JAB) and by the following grants from the National Institutes of Health: Al 35294 (JAB), A135990 (DMK). MDG is supported by the Solomon Papper, M.D. Young Investigator Grant of the National Kidney Foundation and by a Mayo Foundation CR20 Award. A single chain construct derived from the mAb 145-2C11 was kindly provided by Dr. David Segal, National Cancer Institute, NIH, Bethesda, MD, USA. A single chain construct derived from the mAb PV1 was kindly provided by Dr. Mary Collins, Genetics Institute, Cambridge, MD, USA. The authors wish to thank Professor K. Dane Wittrup and his lab for assistance and discussion on the yeast display system.",

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doi = "10.1016/S0022-1759(00)00344-6",

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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.

N1 - Funding Information: This work was supported by a grant from the Roche Organ Transplant Research Foundation (JAB) and by the following grants from the National Institutes of Health: Al 35294 (JAB), A135990 (DMK). MDG is supported by the Solomon Papper, M.D. Young Investigator Grant of the National Kidney Foundation and by a Mayo Foundation CR20 Award. A single chain construct derived from the mAb 145-2C11 was kindly provided by Dr. David Segal, National Cancer Institute, NIH, Bethesda, MD, USA. A single chain construct derived from the mAb PV1 was kindly provided by Dr. Mary Collins, Genetics Institute, Cambridge, MD, USA. The authors wish to thank Professor K. Dane Wittrup and his lab for assistance and discussion on the yeast display system.

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.

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KW - Monoclonal antibodies

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KW - Protein engineering

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JO - Journal of Immunological Methods

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IS - 1-2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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