Development and applications of surface-linked single chain antibodies against T-cell antigens.
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 CD3epsilon, 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.
Griffin
M D
MD
The Ben May Institute for Cancer Research, Dept. of Pathology and Committee on Immunology, University of Chicago, Chicago, IL, USA
Holman
P O
PO
Tang
Q
Q
Ashourian
N
N
Korthäuer
U
U
Kranz
D M
DM
Bluestone
J A
JA
D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex; D060908:CTLA-4 Antigen; D006801:Humans; D018796:Immunoconjugates; D007128:Immunoglobulin Fragments / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D015202:Protein Engineering; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D017252:CD3 Complex; C115335:CD3E protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D007128:Immunoglobulin Fragments; D011948:Receptors, Antigen, T-Cell; C055966:immunoglobulin Fv; D000069594:Abatacept