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

• DOI: 10.1038/s41598-021-99347-0
• Publication Date: 2021-10-05T15:38:54Z
• Authors: 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
• Keywords: Priming (agriculture); Adoptive Cell Transfer; Cell therapy; Cancer Immunotherapy

Adoptive T-cell transfer (ACT) offers a curative therapeutic option for subsets of melanoma and hematological cancer patients. To increase response rates broaden the applicability ACT, it is necessary to improve post-infusion performance transferred T cells. The design improved treatment strategies includes cells with less differentiated phenotype. Such cell have high proliferative potential but require stimulatory signals in vivo differentiate into tumor-reactive effector Thus, combination are needed support implementation Here we show that systemic delivery tumor-associated antigens (TAAs) facilitates priming expansion previously non-activated enhance cytotoxicity activated achieve this priming, use flexible vehicles TAAs TLR7/8 agonist. Contrasting subcutaneous systems, these accumulate spleen, thereby achieving close proximity both cross-presenting dendritic cells, resulting robust anti-tumor reactivity. This TAA platform strategy safely potentiate using low doses antigen agonist, effect ACT.