Multispecific anti-HIV duoCAR-T cells display broad in vitro antiviral activity and potent in vivo elimination of HIV-infected cells in a humanized mouse model

Kim Anthony-Gonda; Ariola Bardhi; Alex Ray; Nina Flerin; Mengyan Li; Weizao Chen; Christina Ochsenbauer; John C. Kappes; Winfried Krueger; Andrew Worden; Dina Schneider; Zhongyu Zhu; Rimas Orentas; Dimiter S. Dimitrov; Harris Goldstein; Boro Dropulić

doi:10.1126/scitranslmed.aav5685

Research ArticleHIV

Multispecific anti-HIV duoCAR-T cells display broad in vitro antiviral activity and potent in vivo elimination of HIV-infected cells in a humanized mouse model

View ORCID ProfileKim Anthony-Gonda¹,*,
View ORCID ProfileAriola Bardhi²,*,
View ORCID ProfileAlex Ray ²,
View ORCID ProfileNina Flerin²,
View ORCID ProfileMengyan Li²,
Weizao Chen³,
View ORCID ProfileChristina Ochsenbauer ⁴,
View ORCID ProfileJohn C. Kappes ⁴,⁵,
View ORCID ProfileWinfried Krueger¹,
View ORCID ProfileAndrew Worden¹,
Dina Schneider¹,
Zhongyu Zhu¹,
View ORCID ProfileRimas Orentas¹,†,
View ORCID ProfileDimiter S. Dimitrov⁶,‡,
View ORCID ProfileHarris Goldstein ²,‡ and
View ORCID ProfileBoro Dropulić¹,‡

¹Lentigen, a Miltenyi Biotec Company, Gaithersburg, MD 20878, USA.
²Department of Microbiology and Immunology and Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
³Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
⁴Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁵Birmingham Veterans Affairs Medical Center, Research Service, Birmingham, AL 35294, USA.
⁶Center for Antibody Therapeutics, University of Pittsburgh, Pittsburgh, PA 15261, USA.

↵‡Corresponding author. Email: boro.dropulic{at}lentigen.com (B.D.); harris.goldstein{at}einstein.yu.edu (H.G.); dsd116{at}pitt.edu (D.S.D.)

↵* These authors contributed equally to this work.
↵† Present address: Ben Towne Center for Childhood Cancer Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA.

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Science Translational Medicine 07 Aug 2019:
Vol. 11, Issue 504, eaav5685
DOI: 10.1126/scitranslmed.aav5685

Kim Anthony-Gonda

1Lentigen, a Miltenyi Biotec Company, Gaithersburg, MD 20878, USA.

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Ariola Bardhi

2Department of Microbiology and Immunology and Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Alex Ray

2Department of Microbiology and Immunology and Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Nina Flerin

2Department of Microbiology and Immunology and Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Mengyan Li

2Department of Microbiology and Immunology and Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Weizao Chen

3Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.

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Christina Ochsenbauer

4Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

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John C. Kappes

4Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

5Birmingham Veterans Affairs Medical Center, Research Service, Birmingham, AL 35294, USA.

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Winfried Krueger

1Lentigen, a Miltenyi Biotec Company, Gaithersburg, MD 20878, USA.

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Andrew Worden

1Lentigen, a Miltenyi Biotec Company, Gaithersburg, MD 20878, USA.

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Dina Schneider

1Lentigen, a Miltenyi Biotec Company, Gaithersburg, MD 20878, USA.

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Zhongyu Zhu

1Lentigen, a Miltenyi Biotec Company, Gaithersburg, MD 20878, USA.

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Rimas Orentas

1Lentigen, a Miltenyi Biotec Company, Gaithersburg, MD 20878, USA.

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Dimiter S. Dimitrov

6Center for Antibody Therapeutics, University of Pittsburgh, Pittsburgh, PA 15261, USA.

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For correspondence: boro.dropulic@lentigen.com harris.goldstein@einstein.yu.edu dsd116@pitt.edu

Harris Goldstein

2Department of Microbiology and Immunology and Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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For correspondence: boro.dropulic@lentigen.com harris.goldstein@einstein.yu.edu dsd116@pitt.edu

Boro Dropulić

1Lentigen, a Miltenyi Biotec Company, Gaithersburg, MD 20878, USA.

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For correspondence: boro.dropulic@lentigen.com harris.goldstein@einstein.yu.edu dsd116@pitt.edu

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Multispecific anti-HIV duoCAR-T cells display broad in vitro antiviral activity and potent in vivo elimination of HIV-infected cells in a humanized mouse model

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