Three-dimensional cell culture of chimeric antigen receptor T cells originated from peripheral blood mononuclear cells towards cellular therapies

Abstract

3D cell culture; CAR T cells; Adoptive cell therapy

Cultiu cel·lular 3D; Cèl·lules T CAR; Teràpia cel·lular adoptiva

Cultivo celular 3D; Células T CAR; Terapia celular adoptiva

Background aims With the objective of improving the ex vivo production of therapeutic chimeric antigen receptor (CAR) T cells, we explored the addition of three-dimensional (3D) polystyrene scaffolds to standard suspension cell cultures. Methods We aimed to mimic the structural support given by the lymph nodes during in vivo lymphocyte expansion. Results We observed an increase in cell proliferation compared with standard suspension systems as well as an enhanced cytotoxicity toward cancer cells. Moreover, we directly obtained the CAR T cells from peripheral blood mononuclear cells, thus minimizing the ex vivo manipulation of the therapeutic cells and opening the way to synergies among different cell populations. Conclusions We propose the use of commercially available 3D polystyrene systems to improve the current immune cell cultures and resulting cell products for emerging cellular (immuno)therapies.

This research was funded by Instituto de Salud Carlos III through Consorcio Centro de Investigación Biomédica en Red (CIBER) with the projects “Alycia” (Nr. BBN18PI01) and “Gels4ACT” (Nr. BBN20PIV02). The authors are also grateful for the financial support received from the Spanish Ministry of Science and Innovation (PID2020-115296RA-I00, PID2019-105622RBI00 and the “Ramón y Cajal” program [RYC-2017-22614]). The work was supported as well by the Max Planck Society through the Max Planck Partner Group “Dynamic Biomimetics for Cancer Immunotherapy” in collaboration with the Max Planck for Medical Research (Heidelberg, Germany). This research was also supported by the European Union's Horizon 2020 research and innovation programme H2020-MSCA-COFUND-2016 (DOC-FAM, grant agreement Nr. 754397). The authors acknowledge financial support from the Spanish Ministry of Science and Innovation through the “Severo Ochoa” Programme for Centres of Excellence in R&D (CEX2019-000917-S).