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| Item Type: | Article |
|---|---|
| Title: | CD3 aptamers promote expansion and persistence of tumor-reactive T cells for adoptive T cell therapy in cancer |
| Creators Name: | Menon, A.P., Villanueva, H., Meraviglia-Crivelli, D., van Santen, H.M., Hellmeier, J., Zheleva, A., Nonateli, F., Peters, T., Wachsmann, T.L.A., Hernandez-Rueda, M., Huppa, J.B., Schütz, G.J., Sevcsik, E., Moreno, B. and Pastor, F. |
| Abstract: | The CD3/T cell receptor (TCR) complex is responsible for antigen-specific pathogen recognition by T cells, and initiates the signaling cascade necessary for activation of effector functions. CD3 agonistic antibodies are commonly used to expand T lymphocytes in a wide range of clinical applications, including in adoptive T cell therapy for cancer patients. A major drawback of expanding T cell populations ex vivo using CD3 agonistic antibodies is that they expand and activate T cells independent of their TCR antigen specificity. Therapeutic agents that facilitate expansion of T cells in an antigen-specific manner and reduce their threshold of T cell activation are therefore of great interest for adoptive T cell therapy protocols. To identify CD3-specific T cell agonists, several RNA aptamers were selected against CD3 using Systematic Evolution of Ligands by EXponential enrichment combined with high-throughput sequencing. The extent and specificity of aptamer binding to target CD3 were assessed through surface plasma resonance, P32 double-filter assays, and flow cytometry. Aptamer-mediated modulation of the threshold of T cell activation was observed in vitro and in preclinical transgenic TCR mouse models. The aptamers improved efficacy and persistence of adoptive T cell therapy by low-affinity TCR-reactive T lymphocytes in melanoma-bearing mice. Thus, CD3-specific aptamers can be applied as therapeutic agents which facilitate the expansion of tumor-reactive T lymphocytes while conserving their tumor specificity. Furthermore, selected CD3 aptamers also exhibit cross-reactivity to human CD3, expanding their potential for clinical translation and application in the future. |
| Keywords: | MT: Oligonucleotides: Therapies and Applications, CD3, Aptamer, Cancer Immunotherapy, Adoptive T Cell Therapy |
| Source: | Molecular Therapy Nucleic Acids |
| ISSN: | 2162-2531 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 35 |
| Number: | 2 |
| Page Range: | 102198 |
| Date: | 11 June 2024 |
| Official Publication: | https://doi.org/10.1016/j.omtn.2024.102198 |
| PubMed: | View item in PubMed |
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