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Lunch & Poster Display session

39P - TCR engaging antigen-scaffolds for targeted expansion of functionally improved T cells for adoptive cell therapy

Date

12 Dec 2019

Session

Lunch & Poster Display session

Presenters

Georgios Kladis

Citation

Annals of Oncology (2019) 30 (suppl_11): xi12-xi15. 10.1093/annonc/mdz448

Authors

G. Kladis1, V. Rafa Mindahl2, T. Tamhane1, A. Kai Bentzen1, M. Donia3, I.M. Svane3, H. Niessner4, T. Sinnberg4, C. Garbe5, S. Nyboe Jacobsen1, C. Schmees6, S. Reker Hadrup2

Author affiliations

  • 1 Dtu Healthtech, Technical University of Denmark, 2800 - Kongens Lyngby/DK
  • 2 Dtu Healthtech, Technical University of Denmark, 1870 - Kongens Lyngby/DK
  • 3 Nationalt Center For Cancer Immunterapi, Ccit-dk, Herlev Hospital, 2730 - Herlev/DK
  • 4 Department Of Dermatology, Universitätsklinikum Tübingen, 72076 - Tübingen/DE
  • 5 Department Of Dermatology, Universitaets-Hautklinik Tuebingen, 72076 - Tuebingen/DE
  • 6 Natural And Medical Sciences Institute, Universitätsklinikum Tübingen, 72076 - Tuebingen/DE
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Resources

Abstract 39P

Background

Precise targeting of patient’s tumor can be facilitated through T cells recognizing specific pMHC complexes on these tumors. Once such antigen landscape is defined, an additional challenge relates to the ability to mount a functional T cell response specific to such antigens. Current T Cell expansion techniques provide no efficient strategy for antigen-specific stimulation and results largely in exhausted T cells. Here we present a new technology for ex-vivo peptide-MHC directed expansion and functional enhancement of T cells, using artificial antigen-presenting scaffolds (Ag-scaffolds).

Methods

Dextran backbone conjugated with streptavidin was used for Ag-scaffold assembly. Such backbone was incubated together with biotinylated MHC class I molecules holding a given peptide (pMHC) and biotinylated human cytokines in various ratios. PBMCs from healthy donors with known virus epitopes and from melanoma patients with known epitopes were expanded for 2 weeks with Ag-scaffold, added when the cell cultures were initiated and twice per week for two weeks. The expansion of antigen-specific CD8 T cells was monitored and analyzed by flow cytometry.

Results

Here we demonstrate the value of the antigen-scaffold based expansion, by the expansion of virus-CD8 T cells from peripheral blood, and tumor-specific T cells from both peripheral blood and tumor site. We can favorably expand both neo- and shared antigen specific T cell populations. The resulting T cell product exhibit a multifunctional cytokine profile upon antigen challenge, high levels of CD28 expression, and reduced levels of PD-1 expression. Importantly, numerous different pMHC-specific T-cell populations can be stimulated in a single culture, and we can obtain better tumor killing properties than conventional TIL-ACT products.

Conclusion

This study presents a new technology for expanding functionally enhanced antigen-specific CD8 T cells suited for implementation to ACT strategies. T cell phenotype and functionality are known to be important parameters in successful adoptive T cell transfer, and hence it´s plausible that antigen scaffold based expanded T cell product may improve treatment outcome compared to conventional expansion strategies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Innovation Fund Denmark.

Disclosure

All authors have declared no conflicts of interest.

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