Dataset Information

Phase I study of intraventricular infusions of autologous ex vivo expanded NK cells in children with recurrent medulloblastoma and ependymoma.

ABSTRACT:

Background

Recurrent pediatric medulloblastoma and ependymoma have a grim prognosis. We report a first-in-human, phase I study of intraventricular infusions of ex vivo expanded autologous natural killer (NK) cells in these tumors, with correlative studies.

Methods

Twelve patients were enrolled, 9 received protocol therapy up to 3 infusions weekly, in escalating doses from 3 × 106 to 3 × 108 NK cells/m2/infusion, for up to 3 cycles. Cerebrospinal fluid (CSF) was obtained for cellular profile, persistence, and phenotypic analysis of NK cells. Radiomic characterization on pretreatment MRI scans was performed in 7 patients, to develop a non-invasive imaging-based signature.

Results

Primary objectives of NK cell harvest, expansion, release, and safety of 112 intraventricular infusions of NK cells were achieved in all 9 patients. There were no dose-limiting toxicities. All patients showed progressive disease (PD), except 1 patient showed stable disease for one month at end of study follow-up. Another patient had transient radiographic response of the intraventricular tumor after 5 infusions of NK cell before progressing to PD. At higher dose levels, NK cells increased in the CSF during treatment with repetitive infusions (mean 11.6-fold). Frequent infusions of NK cells resulted in CSF pleocytosis. Radiomic signatures were profiled in 7 patients, evaluating ability to predict upfront radiographic changes, although they did not attain statistical significance.

Conclusions

This study demonstrated feasibility of production and safety of intraventricular infusions of autologous NK cells. These findings support further investigation of locoregional NK cell infusions in children with brain malignancies.

SUBMITTER: Khatua S

PROVIDER: S-EPMC7594549 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Phase I study of intraventricular infusions of autologous ex vivo expanded NK cells in children with recurrent medulloblastoma and ependymoma.

Khatua Soumen S Cooper Laurence J N LJN Sandberg David I DI Ketonen Leena L Johnson Jason M JM Rytting Michael E ME Liu Diane D DD Meador Heather H Trikha Prashant P Nakkula Robin J RJ Behbehani Gregory K GK Ragoonanan Dristhi D Gupta Sumit S Kotrotsou Aikaterini A Idris Tagwa T Shpall Elizabeth J EJ Rezvani Katy K Colen Rivka R Zaky Wafik W Lee Dean A DA Gopalakrishnan Vidya V

Neuro-oncology 20200801 8

<h4>Background</h4>Recurrent pediatric medulloblastoma and ependymoma have a grim prognosis. We report a first-in-human, phase I study of intraventricular infusions of ex vivo expanded autologous natural killer (NK) cells in these tumors, with correlative studies.<h4>Methods</h4>Twelve patients were enrolled, 9 received protocol therapy up to 3 infusions weekly, in escalating doses from 3 × 106 to 3 × 108 NK cells/m2/infusion, for up to 3 cycles. Cerebrospinal fluid (CSF) was obtained for cellul ...[more]

PMID: 32152626

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Project description:The presence of peritoneal metastasis in patients with pancreatic cancer is associated with poor prognosis. Chemotherapy and radiotherapy may result in poor prognosis in patients with pancreatic cancer. However, immunotherapy improves prognosis even at an advanced stage of the disease. The present study reported a case of a combined therapy of autologous ex vivo expanded natural killer (NK) cells and programmed cell death 1 (PD-1) inhibitor in a patient with pancreatic cancer and peritoneal metastasis. The NK cells were expanded ex vivo and intravenously injected. This was followed by intravenous administration of two dosages of PD-1 inhibitor. Computed tomography and magnetic resonance imaging were performed to assess the size of tumor before and after the combined therapy. In addition, the blood sample and ascites were collected and analyzed before and after the combined therapy. Flow cytometry was carried out to measure the subsets of T cells and macrophages in the collected ascites. Meanwhile, the levels of cytokines in the ascites were quantified through enzyme-linked immunosorbent assay, and Luminex assays were conducted on the supernatant. It was revealed that after the combined therapy, cancer cells disappeared in the ascites, and the T cells were activated, which could be confirmed by the decreased levels of PD-1 and T cell immunoglobulin and mucin domain-containing protein 3. Also, the functioning of macrophages was improved, as shown by the increased level of CD86 and the reduced levels of CD206 and HLA-DR. Notably, the levels of cytokines (transforming growth factor-β, vascular endothelial growth factor, and interleukin-10) in ascites were significantly upregulated after the combined therapy. In conclusion, it was evident that NK cells combined with PD-1 inhibitor improved the immune microenvironment of carcinomatosis in the peritoneal cavity. Therefore, the combined therapy may be beneficial for suppressing pancreatic cancer and the presence of metastases in the peritoneal cavity. However, there is a need for additional randomized studies to confirm the efficacy of combined therapy.

Dataset Information

Phase I study of intraventricular infusions of autologous ex vivo expanded NK cells in children with recurrent medulloblastoma and ependymoma.

Background

Methods

Results

Conclusions

Publications

Phase I study of intraventricular infusions of autologous ex vivo expanded NK cells in children with recurrent medulloblastoma and ependymoma.

Similar Datasets

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