BMC Cancer

Ying et al. BMC Cancer  (2021) 21:198

https://doi.org/10.1186/s12885-021-07934-1

Distribution of chimeric antigen receptor-modified T cells against CD19 in B-cell malignancies

Zhitao Ying, Ting He, Xiaopei Wang, Wen Zheng, Ningjing Lin, Meifeng Tu, Yan Xie, Lingyan Ping, Chen Zhang, Weiping Liu, Lijuan Deng, Meng Wu, Feier Feng, Xin Leng, Tingting Du, Feifei Qi, Xuelian Hu, Yanping Ding, Xin-An Lu, Yuqin Song, Jun Zhu

Abstract

Background: The 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.

Methods: NALM-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.

Results: CAR-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.

Conclusions: CAR-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 registration: The registration date of the clinical trial is May 17, 2018 and the trial registration numbers is NCT03528421 .

Keywords: B-ALL; B-NHL; Biodistribution; Blood; CAR-T.