Enhancing adoptive CD8 T cell therapy by systemic delivery of tumor associated antigens

Ditte E Jæhger, Mie L Hübbe, Martin K Kræmer, Gael Clergeaud, André V Olsen, Camilla Stavnsbjerg, Mette N Wiinholt, Andreas Kjær, Jonas R Henriksen, Anders E Hansen, Thomas L Andresen

Abstract

Adoptive 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.

OriginalsprogEngelsk
Artikelnummer19794
TidsskriftScientific Reports
Vol/bind11
Udgave nummer1
Sider (fra-til)19794
ISSN2045-2322
DOI
StatusUdgivet - 5 okt. 2021

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