Bibliographic Details
| Title: |
CD3 aptamers promote expansion and persistence of tumor-reactive T cells for adoptive T cell therapy in cancer |
| Authors: |
Ashwathi Puravankara Menon, Helena Villanueva, Daniel Meraviglia-Crivelli, Hisse M. van Santen, Joschka Hellmeier, Angelina Zheleva, Francesca Nonateli, Timo Peters, Tassilo L.A. Wachsmann, Mercedes Hernandez-Rueda, Johannes B. Huppa, Gerhard J. Schütz, Eva Sevcsik, Beatriz Moreno, Fernando Pastor |
| Source: |
Molecular Therapy: Nucleic Acids, Vol 35, Iss 2, Pp 102198- (2024) |
| Publisher Information: |
Elsevier, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Therapeutics. Pharmacology |
| Subject Terms: |
MT: Oligonucleotides: Therapies and Applications, CD3, aptamer, cancer immunotherapy, adoptive T cell therapy, Therapeutics. Pharmacology, RM1-950 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2162-2531 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2162253124000854; https://doaj.org/toc/2162-2531 |
| DOI: |
10.1016/j.omtn.2024.102198 |
| Access URL: |
https://doaj.org/article/6c3ef753dfa94901b0ef2480454cb96e |
| Accession Number: |
edsdoj.6c3ef753dfa94901b0ef2480454cb96e |
| Database: |
Directory of Open Access Journals |
