Publicaciones científicas
CD3 aptamers promote expansion and persistence of tumor-reactive T cells for adoptive T cell therapy in cancer
Ashwathi Puravankara Menon 1, Helena Villanueva 1, Daniel Meraviglia-Crivelli 1, Hisse M van Santen 2, Joschka Hellmeier 3, Angelina Zheleva 1, Francesca Nonateli 1, Timo Peters 4, Tassilo L A Wachsmann 5, Mercedes Hernandez-Rueda 1, Johannes B Huppa 4, Gerhard J Schütz 3, Eva Sevcsik 3, Beatriz Moreno 1, Fernando Pastor 1 6 7
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.
CITA DEL ARTÍCULO Mol Ther Nucleic Acids. 2024 Apr 23;35(2):102198. doi: 10.1016/j.omtn.2024.102198. eCollection 2024 Jun 11.
![](/.resources/ModuloCUN/resources/img/publicaciones/icono-destacado-investigadores.png)
Nuestros autores
![Silueta investigadores. Cima Universidad de Navarra](/.imaging/mte/cima/profesional_carrusel-80x80/dam/cima/imagenes/profesionales/silueta-cima/jcr:content/silueta-cima.png)
![Helena Villanueva. Programa Terapias Moleculares. Cima](/.imaging/mte/cima/profesional_carrusel-80x80/dam/cima/imagenes/profesionales/programas-transversales/terapias-moleculares/helena-villanueva-ruiz/jcr:content/helena-villanueva-ruiz.jpg)
![Silueta investigadores. Cima Universidad de Navarra](/.imaging/mte/cima/profesional_carrusel-80x80/dam/cima/imagenes/profesionales/silueta-cima/jcr:content/silueta-cima.png)
![Angelina Zheleva. Investigadora posdoctoral del Grupo de Investigación de Aptámeros.](/.imaging/mte/cima/profesional_carrusel-80x80/dam/cima/imagenes/profesionales/investigadores/zheleva-angelina/jcr:content/zheleva-angelina.jpg)
![Mercedes Hernández. Grupo de Investigación en Terapia Celular Adoptiva. Cima Universidad de Navarra](/.imaging/mte/cima/profesional_carrusel-80x80/dam/cima/imagenes/profesionales/investigadores/hernandez-mercedes/jcr:content/hernandez-mercedes.jpg)
![Beatriz Moreno. Terapias Moleculares. Cima Investigadora del Programa de Terapias Moleculares del Cima Universidad de Navarra](/.imaging/mte/cima/profesional_carrusel-80x80/dam/cima/imagenes/profesionales/programas-transversales/terapias-moleculares/beatriz-moreno-bruna/jcr:content/beatriz-moreno-bruna.jpg)