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- Title
Nanoparticle-based modulation of CD4<sup>+</sup> T cell effector and helper functions enhances adoptive immunotherapy.
- Authors
Isser, Ariel; Silver, Aliyah B.; Pruitt, Hawley C.; Mass, Michal; Elias, Emma H.; Aihara, Gohta; Kang, Si-Sim; Bachmann, Niklas; Chen, Ying-Yu; Leonard, Elissa K.; Bieler, Joan G.; Chaisawangwong, Worarat; Choy, Joseph; Shannon, Sydney R.; Gerecht, Sharon; Weber, Jeffrey S.; Spangler, Jamie B.; Schneck, Jonathan P.
- 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. Adoptive cell therapies (ACT) hold promise for cancer immunotherapy, but optimization is still an ongoing process. Here the authors report CD4-targeted, nanoparticle-based artificial antigen-presenting cells that expand CD4+ T cells capable of lysing tumor cell lysis in vitro, and CD8+ T cells showing antitumor activity in a mouse melanoma model.
- Subjects
CYTOTOXIC T cells; T helper cells; IMMUNE response; T cells; HLA histocompatibility antigens; ANTIGEN presenting cells; LYSIS; ARTIFICIAL cells
- Publication
Nature Communications, 2022, Vol 13, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-33597-y