The Effects of CAR T-cell Therapy on Interleukin 6 and Interleukin 1 Inflammatory Cytokines, and TLR2 and TLR4 Expression in Patients With Dental Implants Who Received the COVID-19 Vaccine

Abstract

Background: COVID-19 is a family of coronaviruses that was started in Wuhan, China in 2020. This virus has a strong relationship with cytokine storm. The aim of this novel study was to evaluate the chimeric antigen receptor (CAR) T-cell therapy drug’s effects on immunity member expression in dental implant patients who received the COVID-19 vaccine. Methods: A total of ten patients who received the COVID-19 vaccine and applied for dental implants were chosen for this study. Five patients who applied for dental implants but did not receive the COVID-19 vaccine were selected as the control group. The macrophage cells were isolated from dental pulp and treated with CAR T-cell therapy drugs. The real-time polymerase chain reaction was performed for the evaluation of Toll-like receptor 2 (TLR2) and TLR4 expression, and an enzyme-linked immunosorbent assay was used to determine the levels of interleukin (IL-6) and IL-1 cytokines. Results: The results of the present study showed that 48 hours after treating the cells with CAR T-cell therapy drugs, the TLR2 and TLR4 expression and IL-6 and IL-1 levels were decreased, and this amount was higher in the tisagenlecleucel group than in the axicabtagene ciloleucel group (P<0.001). The COVID-19 vaccine group results demonstrated no significant difference compared with other groups. Conclusion: The findings of the present study proved that the drugs as a CAR T-cell therapy, such as Tisagenlecleucel and Axicabtagene ciloleucel, could decrease TLR function and inflammatory cytokines levels, but due to the cytokines storm in COVID-19, these drugs could not affect innate immunity receptors and cytokines levels.