In:
The Journal of Immunology, The American Association of Immunologists, Vol. 210, No. 1_Supplement ( 2023-05-01), p. 250.12-250.12
Abstract:
CD4 T cell-based adoptive cell transfer (ACT) therapies have clinical success across multiple cancer types, including metastatic melanoma and epithelial cancer. One of the challenges of ACT therapy is finding methods to expand tumor antigen-specific T cells ex vivo. Therefore, engineering platforms for antigen-specific T cell expansion are critical since they provide greater control over studying T cell biology and have significant translational relevance. We developed a nanoscale platform that expands murine and human antigen-specific T cells in vitro. This artificial antigen-presenting cells (aAPCs) platform provides T cells with two critical signals, MHC class II and anti-CD28, for T cell activation, which permits the activation of cognate antigen-specific CD4 T cells ex vivo. We isolate human CD4 T cells from PBMCs of healthy donors who are HLA DP4 +. We then stimulate CD4 T cells with aAPCs in media with inflammatory cytokine and access the specificity and effector function through tetramer staining, cytokine release assays, and killing assays. Co-culturing aAPCs and human CD4 T cells significantly increase the frequency of cognate antigen-specific CD4 T cells. Specifically, we expanded tetanus toxin-specific HLA-DP4 +CD4 T cells from healthy human PBMCs with aAPC. By the end of the expansion, the antigen-specific expanded from less than 1% to over 40% by day 21. In addition, the resulting antigen-specific cells display high levels of effector cytokine production, including TNF-a, IFN-g, IL-2, and granzyme B. Consistently, aAPC-activated CD4 T cells demonstrate robust lytic capacity in vitroand in vivo. These data show that aAPC can expand antigen-specific human cytotoxic CD4 T cells from a rare precursor population.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.210.Supp.250.12
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2023
detail.hit.zdb_id:
1475085-5
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