» Articles » PMID: 7889540

A Universal Antibody-derived Targeting Agent

Overview
Journal Cell Biophys
Specialty Biophysics
Date 1993 Jan 1
PMID 7889540
Authors
Affiliations
Soon will be listed here.
Abstract

We report bacterial expression of a single-chain antibody (ScFv) reactive against the haptens 4-hydroxy-3 nitrophenylacetic acid (NP) and 4-hydroxy-3-iodo-5-nitrophenylacetic acid (NIP) that is suitable for targeting to mammalian cells in vitro in a novel two-step targeting strategy. Hapten-derivatized primary antibodies of known specificity, bound to target cells, can capture the ScFv. Specificity resides in the interaction of the primary targeting antibody with the target and the interaction of the ScFv for NP/NIP, since the ScFv does not bind cells and nonderivatized antibodies bound at cells cannot capture the ScFv. The ScFv described here can therefore be considered as a universal agent for delivery of drugs, toxins, or radionuclides to any cell type for which a previously characterized antibody exists.

References
1.
Glockshuber R, Malia M, Pfitzinger I, Pluckthun A . A comparison of strategies to stabilize immunoglobulin Fv-fragments. Biochemistry. 1990; 29(6):1362-7. DOI: 10.1021/bi00458a002. View

2.
Yokota T, Milenic D, Whitlow M, Schlom J . Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms. Cancer Res. 1992; 52(12):3402-8. View

3.
Senter P, Saulnier M, Schreiber G, Hirschberg D, Brown J, Hellstrom I . Anti-tumor effects of antibody-alkaline phosphatase conjugates in combination with etoposide phosphate. Proc Natl Acad Sci U S A. 1988; 85(13):4842-6. PMC: 280532. DOI: 10.1073/pnas.85.13.4842. View

4.
Mariani M, Bracci L, Presentini R, Nucci D, Neri P, Antoni G . Immunogenicity of a free synthetic peptide: carrier-conjugation enhances antibody affinity for the native protein. Mol Immunol. 1987; 24(3):297-303. DOI: 10.1016/0161-5890(87)90148-9. View

5.
Chaudhary V, Queen C, Junghans R, Waldmann T, Fitzgerald D, Pastan I . A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin. Nature. 1989; 339(6223):394-7. DOI: 10.1038/339394a0. View