Author:
Jæhger Ditte E.,Hübbe Mie L.,Kræmer Martin K.,Clergeaud Gael,Olsen André V.,Stavnsbjerg Camilla,Wiinholt Mette N.,Kjær Andreas,Henriksen Jonas R.,Hansen Anders E.,Andresen Thomas L.
Abstract
AbstractAdoptive T-cell transfer (ACT) offers a curative therapeutic option for subsets of melanoma and hematological cancer patients. To increase response rates and broaden the applicability of ACT, it is necessary to improve the post-infusion performance of the transferred T cells. The design of improved treatment strategies includes transfer of cells with a less differentiated phenotype. Such T cell subsets have high proliferative potential but require stimulatory signals in vivo to differentiate into tumor-reactive effector T cells. Thus, combination strategies are needed to support the therapeutic implementation of less differentiated T cells. Here we show that systemic delivery of tumor-associated antigens (TAAs) facilitates in vivo priming and expansion of previously non-activated T cells and enhance the cytotoxicity of activated T cells. To achieve this in vivo priming, we use flexible delivery vehicles of TAAs and a TLR7/8 agonist. Contrasting subcutaneous delivery systems, these vehicles accumulate TAAs in the spleen, thereby achieving close proximity to both cross-presenting dendritic cells and transferred T cells, resulting in robust T-cell expansion and anti-tumor reactivity. This TAA delivery platform offers a strategy to safely potentiate the post-infusion performance of T cells using low doses of antigen and TLR7/8 agonist, and thereby enhance the effect of ACT.
Funder
H2020 European Research Council
The Lundbeck Foundation Fellowship Grant
The Novo Foundation Synergy Grant
The Danish Research Council for Independent Research Sapere Aude grant
Publisher
Springer Science and Business Media LLC
Cited by
5 articles.
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