Higher cytotoxicity of divalent antibody-toxins than monovalent antibody-toxins

Jae Seon Won; Pil Won Nam; Yong Chan Lee; Mu Hyeon Choe

doi:10.1016/j.bbrc.2009.02.091

Higher cytotoxicity of divalent antibody-toxins than monovalent antibody-toxins

Jae Seon Won, Pil Won Nam, Yong Chan Lee, Mu Hyeon Choe

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

3 Citations (Scopus)

Abstract

Recombinant antibody-toxins are constructed via the fusion of a "carcinoma-specific" antibody fragment to a toxin. Due to the high affinity and high selectivity of the antibody fragments, antibody-toxins can bind to surface antigens on cancer cells and kill them without harming normal cells [L.H. Pai, J.K. Batra, D.J. FitzGerald, M.C. Willingham, I. Pastan, Anti-tumor activities of immunotoxins made of monoclonal antibody B3 and various forms of Pseudomonas exotoxin, Proc. Natl. Acad. Sci. USA 88 (1991) 3358-3362]. In this study, we constructed the antibody-toxin, Fab-SWn-PE38, with SWn (n = 3, 6, 9) sequences containing n-time repeated (G₄S) between the Fab fragment and PE38 (38 kDa truncated form of Pseudomonas exotoxin A). The SWn sequence also harbored one cysteine residue that could form a disulfide bridge between two Fab-SWn-PE38 monomers. We assessed the cytotoxicity of the monovalent (Fab-SWn-PE38), and divalent ([Fab-SWn-PE38]₂) antibody-toxins. The cytotoxicity of the dimer against the CRL1739 cell line was approximately 18.8-fold higher than that of the monomer on the ng/ml scale, which was approximately 37.6-fold higher on the pM scale. These results strongly indicate that divalency provides higher cytotoxicity for an antibody-toxin.

Original language	English
Pages (from-to)	15-20
Number of pages	6
Journal	Biochemical and biophysical research communications
Volume	382
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2009.02.091
Publication status	Published - 2009 Apr 24

Bibliographical note

Funding Information:
This work was supported by a Korea University Grant and the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (No. R01-2006-000-10125-0).

Keywords

Avidity
Cytotoxicity
Divalent antibody-toxin
Pseudomonas exotoxin A
Recombinant antibody refolding

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2009.02.091

Cite this

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title = "Higher cytotoxicity of divalent antibody-toxins than monovalent antibody-toxins",

abstract = "Recombinant antibody-toxins are constructed via the fusion of a {"}carcinoma-specific{"} antibody fragment to a toxin. Due to the high affinity and high selectivity of the antibody fragments, antibody-toxins can bind to surface antigens on cancer cells and kill them without harming normal cells [L.H. Pai, J.K. Batra, D.J. FitzGerald, M.C. Willingham, I. Pastan, Anti-tumor activities of immunotoxins made of monoclonal antibody B3 and various forms of Pseudomonas exotoxin, Proc. Natl. Acad. Sci. USA 88 (1991) 3358-3362]. In this study, we constructed the antibody-toxin, Fab-SWn-PE38, with SWn (n = 3, 6, 9) sequences containing n-time repeated (G4S) between the Fab fragment and PE38 (38 kDa truncated form of Pseudomonas exotoxin A). The SWn sequence also harbored one cysteine residue that could form a disulfide bridge between two Fab-SWn-PE38 monomers. We assessed the cytotoxicity of the monovalent (Fab-SWn-PE38), and divalent ([Fab-SWn-PE38]2) antibody-toxins. The cytotoxicity of the dimer against the CRL1739 cell line was approximately 18.8-fold higher than that of the monomer on the ng/ml scale, which was approximately 37.6-fold higher on the pM scale. These results strongly indicate that divalency provides higher cytotoxicity for an antibody-toxin.",

keywords = "Avidity, Cytotoxicity, Divalent antibody-toxin, Pseudomonas exotoxin A, Recombinant antibody refolding",

author = "Won, {Jae Seon} and Nam, {Pil Won} and Lee, {Yong Chan} and Choe, {Mu Hyeon}",

note = "Funding Information: This work was supported by a Korea University Grant and the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (No. R01-2006-000-10125-0).",

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AU - Won, Jae Seon

AU - Nam, Pil Won

AU - Lee, Yong Chan

AU - Choe, Mu Hyeon

N1 - Funding Information: This work was supported by a Korea University Grant and the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (No. R01-2006-000-10125-0).

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N2 - Recombinant antibody-toxins are constructed via the fusion of a "carcinoma-specific" antibody fragment to a toxin. Due to the high affinity and high selectivity of the antibody fragments, antibody-toxins can bind to surface antigens on cancer cells and kill them without harming normal cells [L.H. Pai, J.K. Batra, D.J. FitzGerald, M.C. Willingham, I. Pastan, Anti-tumor activities of immunotoxins made of monoclonal antibody B3 and various forms of Pseudomonas exotoxin, Proc. Natl. Acad. Sci. USA 88 (1991) 3358-3362]. In this study, we constructed the antibody-toxin, Fab-SWn-PE38, with SWn (n = 3, 6, 9) sequences containing n-time repeated (G4S) between the Fab fragment and PE38 (38 kDa truncated form of Pseudomonas exotoxin A). The SWn sequence also harbored one cysteine residue that could form a disulfide bridge between two Fab-SWn-PE38 monomers. We assessed the cytotoxicity of the monovalent (Fab-SWn-PE38), and divalent ([Fab-SWn-PE38]2) antibody-toxins. The cytotoxicity of the dimer against the CRL1739 cell line was approximately 18.8-fold higher than that of the monomer on the ng/ml scale, which was approximately 37.6-fold higher on the pM scale. These results strongly indicate that divalency provides higher cytotoxicity for an antibody-toxin.

AB - Recombinant antibody-toxins are constructed via the fusion of a "carcinoma-specific" antibody fragment to a toxin. Due to the high affinity and high selectivity of the antibody fragments, antibody-toxins can bind to surface antigens on cancer cells and kill them without harming normal cells [L.H. Pai, J.K. Batra, D.J. FitzGerald, M.C. Willingham, I. Pastan, Anti-tumor activities of immunotoxins made of monoclonal antibody B3 and various forms of Pseudomonas exotoxin, Proc. Natl. Acad. Sci. USA 88 (1991) 3358-3362]. In this study, we constructed the antibody-toxin, Fab-SWn-PE38, with SWn (n = 3, 6, 9) sequences containing n-time repeated (G4S) between the Fab fragment and PE38 (38 kDa truncated form of Pseudomonas exotoxin A). The SWn sequence also harbored one cysteine residue that could form a disulfide bridge between two Fab-SWn-PE38 monomers. We assessed the cytotoxicity of the monovalent (Fab-SWn-PE38), and divalent ([Fab-SWn-PE38]2) antibody-toxins. The cytotoxicity of the dimer against the CRL1739 cell line was approximately 18.8-fold higher than that of the monomer on the ng/ml scale, which was approximately 37.6-fold higher on the pM scale. These results strongly indicate that divalency provides higher cytotoxicity for an antibody-toxin.

KW - Avidity

KW - Cytotoxicity

KW - Divalent antibody-toxin

KW - Pseudomonas exotoxin A

KW - Recombinant antibody refolding

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JO - Biochemical and biophysical research communications

JF - Biochemical and biophysical research communications

IS - 1

ER -

Higher cytotoxicity of divalent antibody-toxins than monovalent antibody-toxins

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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