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*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

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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.

Original languageEnglish
Article number19794
JournalScientific Reports
Volume11
Issue number1
Number of pages19
ISSN2045-2322
DOIs
Publication statusPublished - 2021

Bibliographical note

Funding Information:
This work was supported by a European council Grant (ERC-2012-StG_20111109), The Lundbeck Foundation Fellowship Grant, The Novo Foundation Synergy Grant and the Danish Research Council for Independent Research Sapere Aude Grant.

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