Rapid In Vivo Screening of Monoclonal Antibody Cocktails Using Hydrodynamic Delivery of DNA-Encoded Modified Antibodies

Hugues Fausther-Bovendo; George Babuadze; Teodora Ivanciuc; Birte Kalveram; Yue Qu; Jihae Choi; Allison McGeer; Mario Ostrowski; Samira Mubareka; Ami Patel; Roberto P. Garofalo; Robert Kozak; Gary P. Kobinger

doi:10.3390/biomedicines13030637

Rapid In Vivo Screening of Monoclonal Antibody Cocktails Using Hydrodynamic Delivery of DNA-Encoded Modified Antibodies

Hugues Fausther-Bovendo
, George Babuadze
, Teodora Ivanciuc
, Birte Kalveram
, Yue Qu
, Jihae Choi
, Allison McGeer
, Mario Ostrowski
, Samira Mubareka
, Ami Patel
, Roberto P. Garofalo
, Robert Kozak
, Gary P. Kobinger

University of Texas Medical Branch at Galveston
Wistar Institute
University of Toronto

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

Abstract

Background: Monoclonal antibodies (mAbs) are potent treatment options for infectious diseases. The rapid isolation and in vivo validation of therapeutic mAb candidates, including mAb cocktails, are essential to combat novel or rapidly mutating pathogens. The rapid selection and production of mAb candidates in sufficient amount and quality for preclinical studies are a major limiting step in the mAb development pipeline.

Methods: Here, we developed a method to facilitate the screening of therapeutic mAbs in mouse models. Four conventional mAbs were transformed into single-chain variable fragments fused to the fragment crystallizable (Fc) region of a human IgG1 (scFv-IgG). These scFv-IgG were expressed individually or as a cocktail in vitro and in mice following transfection or hydrodynamic delivery of the corresponding plasmids. Results: This method induced high expression of all scFv-IgG and provided protection in two murine infection models.

Conclusions: This study highlights the benefits of this approach for the rapid, low-cost screening of therapeutic mAb candidates.

Original language	English
Article number	637
Journal	Biomedicines
Volume	13
Issue number	3
DOIs	https://doi.org/10.3390/biomedicines13030637
Publication status	Published - 5 Mar 2025
Externally published	Yes

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

DNA-encoded antibody
in vivo screening
monoclonal antibodies cocktail

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10.3390/biomedicines13030637Licence: CC BY

Cite this

Fausther-Bovendo, H., Babuadze, G., Ivanciuc, T., Kalveram, B., Qu, Y., Choi, J., McGeer, A., Ostrowski, M., Mubareka, S., Patel, A., Garofalo, R. P., Kozak, R., & Kobinger, G. P. (2025). Rapid In Vivo Screening of Monoclonal Antibody Cocktails Using Hydrodynamic Delivery of DNA-Encoded Modified Antibodies. Biomedicines, 13(3), Article 637. https://doi.org/10.3390/biomedicines13030637

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title = "Rapid In Vivo Screening of Monoclonal Antibody Cocktails Using Hydrodynamic Delivery of DNA-Encoded Modified Antibodies",

abstract = "Background: Monoclonal antibodies (mAbs) are potent treatment options for infectious diseases. The rapid isolation and in vivo validation of therapeutic mAb candidates, including mAb cocktails, are essential to combat novel or rapidly mutating pathogens. The rapid selection and production of mAb candidates in sufficient amount and quality for preclinical studies are a major limiting step in the mAb development pipeline. Methods: Here, we developed a method to facilitate the screening of therapeutic mAbs in mouse models. Four conventional mAbs were transformed into single-chain variable fragments fused to the fragment crystallizable (Fc) region of a human IgG1 (scFv-IgG). These scFv-IgG were expressed individually or as a cocktail in vitro and in mice following transfection or hydrodynamic delivery of the corresponding plasmids. Results: This method induced high expression of all scFv-IgG and provided protection in two murine infection models. Conclusions: This study highlights the benefits of this approach for the rapid, low-cost screening of therapeutic mAb candidates.",

keywords = "DNA-encoded antibody, in vivo screening, monoclonal antibodies cocktail",

author = "Hugues Fausther-Bovendo and George Babuadze and Teodora Ivanciuc and Birte Kalveram and Yue Qu and Jihae Choi and Allison McGeer and Mario Ostrowski and Samira Mubareka and Ami Patel and Garofalo, \{Roberto P.\} and Robert Kozak and Kobinger, \{Gary P.\}",

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doi = "10.3390/biomedicines13030637",

language = "English",

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Fausther-Bovendo, H, Babuadze, G, Ivanciuc, T, Kalveram, B, Qu, Y, Choi, J, McGeer, A, Ostrowski, M, Mubareka, S, Patel, A, Garofalo, RP, Kozak, R & Kobinger, GP 2025, 'Rapid In Vivo Screening of Monoclonal Antibody Cocktails Using Hydrodynamic Delivery of DNA-Encoded Modified Antibodies', Biomedicines, vol. 13, no. 3, 637. https://doi.org/10.3390/biomedicines13030637

TY - JOUR

T1 - Rapid In Vivo Screening of Monoclonal Antibody Cocktails Using Hydrodynamic Delivery of DNA-Encoded Modified Antibodies

AU - Fausther-Bovendo, Hugues

AU - Babuadze, George

AU - Ivanciuc, Teodora

AU - Kalveram, Birte

AU - Qu, Yue

AU - Choi, Jihae

AU - McGeer, Allison

AU - Ostrowski, Mario

AU - Mubareka, Samira

AU - Patel, Ami

AU - Garofalo, Roberto P.

AU - Kozak, Robert

AU - Kobinger, Gary P.

PY - 2025/3/5

Y1 - 2025/3/5

N2 - Background: Monoclonal antibodies (mAbs) are potent treatment options for infectious diseases. The rapid isolation and in vivo validation of therapeutic mAb candidates, including mAb cocktails, are essential to combat novel or rapidly mutating pathogens. The rapid selection and production of mAb candidates in sufficient amount and quality for preclinical studies are a major limiting step in the mAb development pipeline. Methods: Here, we developed a method to facilitate the screening of therapeutic mAbs in mouse models. Four conventional mAbs were transformed into single-chain variable fragments fused to the fragment crystallizable (Fc) region of a human IgG1 (scFv-IgG). These scFv-IgG were expressed individually or as a cocktail in vitro and in mice following transfection or hydrodynamic delivery of the corresponding plasmids. Results: This method induced high expression of all scFv-IgG and provided protection in two murine infection models. Conclusions: This study highlights the benefits of this approach for the rapid, low-cost screening of therapeutic mAb candidates.

AB - Background: Monoclonal antibodies (mAbs) are potent treatment options for infectious diseases. The rapid isolation and in vivo validation of therapeutic mAb candidates, including mAb cocktails, are essential to combat novel or rapidly mutating pathogens. The rapid selection and production of mAb candidates in sufficient amount and quality for preclinical studies are a major limiting step in the mAb development pipeline. Methods: Here, we developed a method to facilitate the screening of therapeutic mAbs in mouse models. Four conventional mAbs were transformed into single-chain variable fragments fused to the fragment crystallizable (Fc) region of a human IgG1 (scFv-IgG). These scFv-IgG were expressed individually or as a cocktail in vitro and in mice following transfection or hydrodynamic delivery of the corresponding plasmids. Results: This method induced high expression of all scFv-IgG and provided protection in two murine infection models. Conclusions: This study highlights the benefits of this approach for the rapid, low-cost screening of therapeutic mAb candidates.

KW - DNA-encoded antibody

KW - in vivo screening

KW - monoclonal antibodies cocktail

U2 - 10.3390/biomedicines13030637

DO - 10.3390/biomedicines13030637

M3 - Article

AN - SCOPUS:105001227494

SN - 2227-9059

VL - 13

JO - Biomedicines

JF - Biomedicines

IS - 3

M1 - 637

ER -

Rapid In Vivo Screening of Monoclonal Antibody Cocktails Using Hydrodynamic Delivery of DNA-Encoded Modified Antibodies

Abstract

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Keywords

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