Nanoparticle-based modulation of CD4+ T cell effector and helper functions enhances adoptive immunotherapy

Ariel Isser; Aliyah B Silver; Hawley C Pruitt; Michal Mass; Emma H Elias; Gohta Aihara; Si-Sim Kang; Niklas Bachmann; Ying-Yu Chen; Elissa K Leonard; Joan G Bieler; Worarat Chaisawangwong; Joseph Choy; Sydney R Shannon; Sharon Gerecht; Jeffrey S Weber; Jamie B Spangler; Jonathan P Schneck

doi:10.1038/s41467-022-33597-y

Nanoparticle-based modulation of CD4⁺ T cell effector and helper functions enhances adoptive immunotherapy

Nat Commun. 2022 Oct 14;13(1):6086. doi: 10.1038/s41467-022-33597-y.

Authors

Ariel Isser^{1

2}, Aliyah B Silver^{2

3

4}, Hawley C Pruitt^{5

6}, Michal Mass^{1

4}, Emma H Elias⁷, Gohta Aihara¹, Si-Sim Kang⁸, Niklas Bachmann⁸, Ying-Yu Chen⁸, Elissa K Leonard^{1

2

4}, Joan G Bieler^{2

8}, Worarat Chaisawangwong^{2

8}, Joseph Choy^{2

4

6

9}, Sydney R Shannon^{1

2

4}, Sharon Gerecht^{1

5

6

9

10}, Jeffrey S Weber¹¹, Jamie B Spangler^{1

4

5

9

10

12

13}, Jonathan P Schneck^{14

15

16

17

18}

Affiliations

¹ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
² Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
³ Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, 21287, USA.
⁴ Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁵ Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21287, USA.
⁶ Institute for NanoBioTechnology, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21287, USA.
⁷ Department of Biology, Johns Hopkins University Krieger School of Arts and Sciences, Baltimore, MD, 21287, USA.
⁸ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁹ Department of Materials Science and Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21287, USA.
¹⁰ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
¹¹ Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY, 10016, USA.
¹² Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
¹³ Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
¹⁴ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. jschnec1@jhmi.edu.
¹⁵ Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. jschnec1@jhmi.edu.
¹⁶ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. jschnec1@jhmi.edu.
¹⁷ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. jschnec1@jhmi.edu.
¹⁸ Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. jschnec1@jhmi.edu.

Abstract

Helper (CD4⁺) T cells perform direct therapeutic functions and augment responses of cells such as cytotoxic (CD8⁺) T cells against a wide variety of diseases and pathogens. Nevertheless, inefficient synthetic technologies for expansion of antigen-specific CD4⁺ T cells hinders consistency and scalability of CD4⁺ T cell-based therapies, and complicates mechanistic studies. Here we describe a nanoparticle platform for ex vivo CD4⁺ T cell culture that mimics antigen presenting cells (APC) through display of major histocompatibility class II (MHC II) molecules. When combined with soluble co-stimulation signals, MHC II artificial APCs (aAPCs) expand cognate murine CD4⁺ T cells, including rare endogenous subsets, to induce potent effector functions in vitro and in vivo. Moreover, MHC II aAPCs provide help signals that enhance antitumor function of aAPC-activated CD8⁺ T cells in a mouse tumor model. Lastly, human leukocyte antigen class II-based aAPCs expand rare subsets of functional, antigen-specific human CD4⁺ T cells. Overall, MHC II aAPCs provide a promising approach for harnessing targeted CD4⁺ T cell responses.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigen-Presenting Cells
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
HLA Antigens
Humans
Immunotherapy, Adoptive*
Mice
Nanoparticles*

Substances

HLA Antigens

Abstract

Publication types

MeSH terms

Substances

Grants and funding