TCR-mimic bispecific antibodies to target the HIV-1 reservoir-Reference-Cited by-同舟云学术

TCR-mimic bispecific antibodies to target the HIV-1 reservoir

Published:2022-04-08 Issue:15 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Sengupta Srona¹²,Board Nathan L.¹,Wu Fengting¹^ORCID,Moskovljevic Milica¹,Douglass Jacqueline³⁴,Zhang Josephine¹,Reinhold Bruce R.⁵⁶⁷,Duke-Cohan Jonathan⁵⁶⁷^ORCID,Yu Jeanna¹,Reed Madison C.¹^ORCID,Tabdili Yasmine¹,Azurmendi Aitana⁸,Fray Emily J.¹^ORCID,Zhang Hao⁹,Hsiue Emily Han-Chung³⁴,Jenike Katharine¹,Ho Ya-Chi¹⁰,Gabelli Sandra B.⁸^ORCID,Kinzler Kenneth W.³⁴¹¹,Vogelstein Bert³⁴¹¹¹²,Zhou Shibin³⁴¹¹,Siliciano Janet D.¹,Sadegh-Nasseri Scheherazade²^ORCID,Reinherz Ellis L.⁵⁶⁷^ORCID,Siliciano Robert F.¹¹²^ORCID

Affiliation:

1. Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205

2. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205

3. Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287

4. Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287

5. Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115

6. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115

7. Department of Medicine, Harvard Medical School, Boston, MA 02115

8. Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21287

9. Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205

10. Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06519

11. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287

12. HHMI, The Johns Hopkins University School of Medicine, Baltimore, MD 21205

Abstract

Significance Novel approaches to promote killing of HIV-1–infected cells are necessary for elimination of the latent reservoir, the main barrier to a cure. Here, we utilized a diverse phage-display library to construct T cell receptor (TCR)-mimic antibodies to HIV-1 peptide-major histocompatibility complexes (pMHC). We show that single-chain diabody forms of these antibodies recognize distinct epitopes in Gag and reverse transcriptase in a specific manner and induce T cell-mediated killing of HIV-1–infected CD4 + T cells. This study lays the groundwork for future exploration of pMHC-based immunotherapeutic approaches toward elimination of the latent reservoir once effective latency-reversing strategies are developed.

Funder

Howard Hughes Medical Institute

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2123406119

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