Dataset Information

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

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 .

SUBMITTER: Ying Z

PROVIDER: S-EPMC7908740 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Ying Zhitao Z He Ting T Wang Xiaopei X Zheng Wen W Lin Ningjing N Tu Meifeng M Xie Yan Y Ping Lingyan L Zhang Chen C Liu Weiping W Deng Lijuan L Wu Meng M Feng Feier F Leng Xin X Du Tingting T Qi Feifei F Hu Xuelian X Ding Yanping Y Lu Xin-An XA Song Yuqin Y Zhu Jun J

BMC cancer 20210225 1

<h4>Background</h4>The unprecedented efficacy of chimeric antigen receptor T (CAR-T) cell immunotherapy of CD19<sup>+</sup> 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.<h4>Methods</h4>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 m ...[more]

PMID: 33632155

Similar Datasets

Project description:BackgroundChimeric antigen receptor (CAR) T cells directed against CD19 (CART19) are effective in B-cell malignancies, but little is known about the molecular factors predicting clinical outcome of CART19 therapy. The increasingly recognized relevance of epigenetic changes in cancer immunology prompted us to determine the impact of the DNA methylation profiles of CART19 cells on the clinical course.MethodsWe recruited 114 patients with B-cell malignancies, comprising 77 patients with acute lymphoblastic leukemia and 37 patients with non-Hodgkin lymphoma who were treated with CART19 cells. Using a comprehensive DNA methylation microarray, we determined the epigenomic changes that occur in the patient T cells upon transduction of the CAR vector. The effects of the identified DNA methylation sites on clinical response, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, event-free survival, and overall survival were assessed. All statistical tests were 2-sided.ResultsWe identified 984 genomic sites with differential DNA methylation between CAR-untransduced and CAR-transduced T cells before infusion into the patient. Eighteen of these distinct epigenetic loci were associated with complete response (CR), adjusting by multiple testing. Using the sites linked to CR, an epigenetic signature, referred to hereafter as the EPICART signature, was established in the initial discovery cohort (n = 79), which was associated with CR (Fisher exact test, P < .001) and enhanced event-free survival (hazard ratio [HR] = 0.36; 95% confidence interval [CI] = 0.19 to 0.70; P = .002; log-rank P = .003) and overall survival (HR = 0.45; 95% CI = 0.20 to 0.99; P = .047; log-rank P = .04;). Most important, the EPICART profile maintained its clinical course predictive value in the validation cohort (n = 35), where it was associated with CR (Fisher exact test, P < .001) and enhanced overall survival (HR = 0.31; 95% CI = 0.11 to 0.84; P = .02; log-rank P = .02).ConclusionsWe show that the DNA methylation landscape of patient CART19 cells influences the efficacy of the cellular immunotherapy treatment in patients with B-cell malignancy.

Dataset Information

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

Background

Methods

Results

Conclusions

Trial registration

Publications

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

Similar Datasets

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