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

• Published in: BMC cancer Vol. 21; no. 1; pp. 198 - 10
• Main Authors: Ying, Zhitao, He, Ting, Wang, Xiaopei, Zheng, Wen, Lin, Ningjing, Tu, Meifeng, Xie, Yan, Ping, Lingyan, Zhang, Chen, Liu, Weiping, Deng, Lijuan, Wu, Meng, Feng, Feier, Leng, Xin, Du, Tingting, Qi, Feifei, Hu, Xuelian, Ding, Yanping, Lu, Xin-An, Song, Yuqin, Zhu, Jun
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.02.2021; BioMed Central; BMC
• Subjects: Acute lymphoblastic leukemia; Adult; Animals; Anticoagulants; Antigen receptors, T cell; Antigens; Antigens, CD19 - immunology; B-ALL; B-NHL; Biodistribution; Blood; Blood diseases; CAR-T; Care and treatment; CD19 antigen; Cell culture; Cell Line, Tumor; Cell therapy; Chimeric antigen receptors; Clinical trials; Development and progression; FDA approval; Female; Flow cytometry; Genetic aspects; Health aspects; Humans; Immunotherapy; Immunotherapy, Adoptive - methods; Leukemia, B-Cell - therapy; Lymphatic leukemia; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoma, B-Cell - therapy; Male; Methods; Mice; Non-Hodgkin's lymphoma; Patient outcomes; Patients; Peripheral blood; Pharmaceuticals; Plasmids; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Receptors; Receptors, Chimeric Antigen - metabolism; Side effects; T cells; Tissue Distribution; Tumors; China; Beijing China; Chicago Illinois; United States > US; B-NHL; B-ALL; CAR-T; Biodistribution; Blood
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-021-07934-1

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