Details

Autor(en) / Beteiligte

• Zhang, David K.Y.
• Vaynrub, Anna
• Mooney, David J.

Titel

Abstract B058: Rapid and controlled T-cell expansion using scaffolds that mimic antigen-presenting cells

Ist Teil von

• Cancer immunology research, 2019-02, Vol.7 (2_Supplement), p.B058-B058

Erscheinungsjahr

2019

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Abstract Current approaches to expand T-cells ex vivo for therapeutic applications are limited by low expansion rates and often result in unpredictable expansion products of varying phenotype and function. Key attributes, such as a balanced ratio of CD4-to-CD8 T-cells, or a high central memory T-cell fraction are known to correlate with robust and durable therapeutic responses but remain difficult to reproducibly achieve. Strategies that allow one to precisely control the phenotype of expanded T-cell products may thus potentiate the effects of CAR-T-cell therapies, and understanding how T-cells respond to stimulation is a crucial step to this end. Recently, we described a 3D expansion system that mimics natural antigen presenting cells (APCs) and promotes greater polyclonal expansion of primary human T-cells than commercial expansion beads (Dynabeads). These biodegradable, APC-mimetic scaffolds (APC-ms) are composed of fluid lipid bilayers supported on mesoporous silica micro-rods, which enables precise control over the spatial organization of membrane-bound T-cell receptor (TCR) stimulatory and costimulatory cues (i.e., anti-CD3/anti-CD28). Here, we investigated the activation and memory signature of primary human T-cells over time in response to APC-ms with different densities of activating surface cues compared to Dynabead stimulation. Higher surface cue densities of anti-CD3/anti-CD28 promoted greater proportions of central memory T-cells, with a parallel increase in the CD4-to-CD8 T-cell ratio. T-cells stimulated with Dynabeads exhibited higher expression of CD25 and CD69 that peaked earlier than standard APC-ms formulations, suggesting that APC-ms promotes relatively more transient T-cell activation than Dynabeads, potentially mitigating overstimulation and exhaustion. Overall, these data demonstrate that APC-ms can be used to rapidly expand primary human T-cells and tune their phenotypic attributes (e.g., CD4-to-CD8 ratio and memory subpopulations). This technology has the potential to improve the production of T-cells for adoptive T-cell-based therapies. Citation Format: David K.Y. Zhang, Anna Vaynrub, David J. Mooney. Rapid and controlled T-cell expansion using scaffolds that mimic antigen-presenting cells [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B058.