Abstract
BackgroundThe unprecedented efficacy of chimeric antigen receptor T (CAR-T) cell immunotherapy of CD19+ B-cell malignancies has opened a new and useful way for the treatment of malignant tumors. Nonetheless, there are still formidable challenges in the field of CAR-T cell therapy, such as the biodistribution of CAR-T cells in vivo.MethodsNALM-6, a human B-cell acute lymphoblastic leukemia (B-ALL) cell line, was used as target cells. CAR-T cells were injected into a mice model with or without target cells. Then we measured the distribution of CAR-T cells in mice. In addition, an exploratory clinical trial was conducted in 13 r/r B-cell non-Hodgkin lymphoma (B-NHL) patients, who received CAR-T cell infusion. The dynamic changes in patient blood parameters over time after infusion were detected by qPCR and flow cytometry.ResultsCAR-T cells still proliferated over time after being infused into the mice without target cells within 2 weeks. However, CAR-T cells did not increase significantly in the presence of target cells within 2 weeks after infusion, but expanded at week 6. In the clinical trial, we found that CAR-T cells peaked at 7–21 days after infusion and lasted for 420 days in peripheral blood of patients. Simultaneously, mild side effects were observed, which could be effectively controlled within 2 months in these patients.ConclusionsCAR-T cells can expand themselves with or without target cells in mice, and persist for a long time in NHL patients without serious side effects.Trial registrationThe registration date of the clinical trial is May 17, 2018 and the trial registration numbers is NCT03528421.
Highlights
The unprecedented efficacy of chimeric antigen receptor T (CAR-T) cell immunotherapy of CD19+ Bcell malignancies has opened a new and useful way for the treatment of malignant tumors
Chimeric Antigen Receptor (CAR)-T cells proliferated without target cells in NCG mice CD19 CAR-T cells containing a 4-1BB co-stimulatory domain that can improve the expansion, persistence and antitumor effect of CAR-T cells [7, 10, 11] (Fig. 1a) were produced by Immunochina Pharmaceuticals following the described process (Fig. 1b)
Most people believed that without target cells in mice, CAR-T cells will disappear in a short time after infusion
Summary
The unprecedented efficacy of chimeric antigen receptor T (CAR-T) cell immunotherapy of CD19+ Bcell malignancies has opened a new and useful way for the treatment of malignant tumors. Chimeric antigen receptor T (CAR-T) cell therapy is drawing more and more attention for treating relapsed or refractory (r/r) B-cell malignancies, including B-cell acute lymphoblastic leukemia (B-ALL) and B-cell nonHodgkin lymphoma (B-NHL) [1,2,3]. The approval of three CAR-T cell products by the US Food and Drug Administration (FDA), Yescarta, Kymriah and Tecartus, have paved the way for the clinical availability of CAR-T cell therapy [4]. There are no available standardized methods for monitoring in vivo behaviors of injected CAR-T cells. Because most of the imaging methods can only monitor the CAR-T cells in a short time, common methods for long-time monitoring are needed
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