Constructs of biotin mimetic peptide with CC49 single-chain Fv designed for tumor pretargeting

Gabriela Pavlinkova; Surinder K. Batra; David Colcher; Barbara J.M. Booth; Janina Baranowska-Kortylewicz

doi:10.1016/S0196-9781(03)00049-4

Constructs of biotin mimetic peptide with CC49 single-chain Fv designed for tumor pretargeting

Gabriela Pavlinkova, Surinder K. Batra, David Colcher, Barbara J.M. Booth, Janina Baranowska-Kortylewicz

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

7 Scopus citations

Abstract

Single-chain Fv constructs comprising a biotin mimetic peptide (BMP) and scFv of CC49 monoclonal antibody were produced to improve pretargeted radioimmunotherapy. BMP units that bind streptavidin were added to the carboxyl terminus of the CC49 V_H region. An engineered scFvBMP monomer and a sc(Fv)₂BMP dimer showed an excellent antigen recognition in vitro with a specific binding of 72±5 and 81±4%, respectively. Properties of ¹²⁵I-sc(Fv)₂BMP in mice bearing LS-174T xenografts were comparable to these of the parent ¹²⁵I-sc(Fv)₂. Complexing of scFvBMPs with streptavidin increased tumor targeting and gave exceptionally high tumor-to-blood values of 63±7 for ¹²⁵I-sc(Fv)₂BMP-streptavidin compared with 37±4 for sc(Fv)₂BMP at 72h after administration. High tumor and negligible normal tissue levels of these novel pretargeting constructs indicate a great potential for pretargeted radioimmunotherapy.

Original language	English (US)
Pages (from-to)	353-362
Number of pages	10
Journal	Peptides
Volume	24
Issue number	3
DOIs	https://doi.org/10.1016/S0196-9781(03)00049-4
State	Published - Mar 1 2003

Keywords

Biotin mimetic peptide
Pretargeting radiotherapy
Single-chain antibody fragments
Streptavidin

ASJC Scopus subject areas

Biochemistry
Physiology
Endocrinology
Cellular and Molecular Neuroscience

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10.1016/S0196-9781(03)00049-4

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title = "Constructs of biotin mimetic peptide with CC49 single-chain Fv designed for tumor pretargeting",

abstract = "Single-chain Fv constructs comprising a biotin mimetic peptide (BMP) and scFv of CC49 monoclonal antibody were produced to improve pretargeted radioimmunotherapy. BMP units that bind streptavidin were added to the carboxyl terminus of the CC49 VH region. An engineered scFvBMP monomer and a sc(Fv)2BMP dimer showed an excellent antigen recognition in vitro with a specific binding of 72±5 and 81±4%, respectively. Properties of 125I-sc(Fv)2BMP in mice bearing LS-174T xenografts were comparable to these of the parent 125I-sc(Fv)2. Complexing of scFvBMPs with streptavidin increased tumor targeting and gave exceptionally high tumor-to-blood values of 63±7 for 125I-sc(Fv)2BMP-streptavidin compared with 37±4 for sc(Fv)2BMP at 72h after administration. High tumor and negligible normal tissue levels of these novel pretargeting constructs indicate a great potential for pretargeted radioimmunotherapy.",

keywords = "Biotin mimetic peptide, Pretargeting radiotherapy, Single-chain antibody fragments, Streptavidin",

author = "Gabriela Pavlinkova and Batra, {Surinder K.} and David Colcher and Booth, {Barbara J.M.} and Janina Baranowska-Kortylewicz",

note = "Funding Information: We thank Ms. K. Devish, and Mr. J. Jokerst for their expert technical assistance. We acknowledge the Molecular Biology Core Lab for sequencing studies and the Monoclonal Antibody Core Facility for their expertise. Grants from the American Cancer Society Institutional Research Grant (WBS 36-5301-2069-001) and the United States Department of Energy (DE-FG02-95ER62024) supported these studies.",

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AU - Pavlinkova, Gabriela

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AU - Colcher, David

AU - Booth, Barbara J.M.

AU - Baranowska-Kortylewicz, Janina

N1 - Funding Information: We thank Ms. K. Devish, and Mr. J. Jokerst for their expert technical assistance. We acknowledge the Molecular Biology Core Lab for sequencing studies and the Monoclonal Antibody Core Facility for their expertise. Grants from the American Cancer Society Institutional Research Grant (WBS 36-5301-2069-001) and the United States Department of Energy (DE-FG02-95ER62024) supported these studies.

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N2 - Single-chain Fv constructs comprising a biotin mimetic peptide (BMP) and scFv of CC49 monoclonal antibody were produced to improve pretargeted radioimmunotherapy. BMP units that bind streptavidin were added to the carboxyl terminus of the CC49 VH region. An engineered scFvBMP monomer and a sc(Fv)2BMP dimer showed an excellent antigen recognition in vitro with a specific binding of 72±5 and 81±4%, respectively. Properties of 125I-sc(Fv)2BMP in mice bearing LS-174T xenografts were comparable to these of the parent 125I-sc(Fv)2. Complexing of scFvBMPs with streptavidin increased tumor targeting and gave exceptionally high tumor-to-blood values of 63±7 for 125I-sc(Fv)2BMP-streptavidin compared with 37±4 for sc(Fv)2BMP at 72h after administration. High tumor and negligible normal tissue levels of these novel pretargeting constructs indicate a great potential for pretargeted radioimmunotherapy.

AB - Single-chain Fv constructs comprising a biotin mimetic peptide (BMP) and scFv of CC49 monoclonal antibody were produced to improve pretargeted radioimmunotherapy. BMP units that bind streptavidin were added to the carboxyl terminus of the CC49 VH region. An engineered scFvBMP monomer and a sc(Fv)2BMP dimer showed an excellent antigen recognition in vitro with a specific binding of 72±5 and 81±4%, respectively. Properties of 125I-sc(Fv)2BMP in mice bearing LS-174T xenografts were comparable to these of the parent 125I-sc(Fv)2. Complexing of scFvBMPs with streptavidin increased tumor targeting and gave exceptionally high tumor-to-blood values of 63±7 for 125I-sc(Fv)2BMP-streptavidin compared with 37±4 for sc(Fv)2BMP at 72h after administration. High tumor and negligible normal tissue levels of these novel pretargeting constructs indicate a great potential for pretargeted radioimmunotherapy.

KW - Biotin mimetic peptide

KW - Pretargeting radiotherapy

KW - Single-chain antibody fragments

KW - Streptavidin

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Constructs of biotin mimetic peptide with CC49 single-chain Fv designed for tumor pretargeting

Abstract

Keywords

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