Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share By
Effects of Polybrene and Retronectin As Transduction Enhancers on the Development and Phenotypic Characteristics of Vhh-Based Cd19-Redirected Car T Cells: A Comparative Investigation Publisher Pubmed



Nasiri F1 ; Muhammadnejad S2 ; Rahbarizadeh F1, 3
Authors

Source: Clinical and Experimental Medicine Published:2023


Abstract

Chimeric antigen receptor T cells (CAR T cells) have improved the prognosis of patients with certain hematologic malignancies. However, broader clinical application of this type of therapy is dependent on production protocols. We characterized VHH-based CD19-redirected CAR T cells generated using the transduction enhancers (TEs) polybrene or retronectin. The proliferation rate of activated T cells transduced using polybrene concentrations > 6 mg/mL decreased compared with untreated group. There was a direct relationship between polybrene concentration and transduction efficacy. Moreover, we demonstrated the proliferation of retronectin-transduced T cells increased in a dose-dependent manner (4–20 μg/mL). Whereas, different retronectin concentrations did not mediate a significant increase in T cell transduction rate. Moreover, lentiviral transduction rate was also dependent on the concentration of lentiviruses. At optimized TE concentrations, multiplicity of infection (MOI) of > 10 decreased living T cell transduction rate. Additionally, we demonstrated that CAR T cell phenotype is highly affected by TE type. Naive T cell differentiation to central memory T cell was observed in the beginning of the expansion process and effector memory T cells became the predominant subset in the second week of expansion. Importantly, retronectin increased the proliferation of CAR T cells alongside medicating higher transduction rates, resulting in more naive and central memory T cells. We demonstrated that a higher percentage of CAR T cells were generated using retronectin (with a less differentiated phenotype) making retronectin a more effective TE than polybrene for long-term CAR T cell processing in preclinical or clinical studies. © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Other Related Docs
8. Hurdles in Cancer Immunotherapy, Cancer Immunology: Bench to Bedside Immunotherapy of Cancers# Second Edition (2020)
10. Crispr/Cas9 Revitalizes Adoptive T-Cell Therapy for Cancer Immunotherapy, Journal of Experimental and Clinical Cancer Research (2021)
16. New Approaches in Cancer Immunotherapy: Review Article, Tehran University Medical Journal (2018)
17. Generation of Cd19-Targeted Chimeric Antigen Receptor T Cells, Archives of Iranian Medicine (2019)