Image-guided interventional radiological delivery of chimeric antigen receptor (CAR) T cells for pleural malignancies in a phase I/II clinical trial Journal Article
| Authors: | Ghosn, M.; Cheema, W.; Zhu, A.; Livschitz, J.; Maybody, M.; Boas, F. E.; Santos, E.; Kim, D.; Beattie, J. A.; Offin, M.; Rusch, V. W.; Zauderer, M. G.; Adusumilli, P. S.; Solomon, S. B. |
| Article Title: | Image-guided interventional radiological delivery of chimeric antigen receptor (CAR) T cells for pleural malignancies in a phase I/II clinical trial |
| Abstract: | Objectives: We describe techniques and results of image-guided delivery of mesothelin-targeted chimeric antigen receptor (CAR) T cells in patients with pleural malignancies in a phase I/II trial (ClinicalTrials.gov: NCT02414269). Materials and methods: Patients without a pleural catheter or who lack effusion for insertion of a catheter (31 of 41) were administered intrapleural CAR T cells by interventional radiologists under image guidance by computed tomography or ultrasound. CAR T cells were administered through a needle in an accessible pleural loculation (intracavitary) or following an induced loculated artificial pneumothorax. In patients where intracavitary infusion was not feasible, CAR T cells were injected via percutaneous approach either surrounding and/or in the pleural nodule/thickening (intratumoral). Pre- and post-procedural clinical, laboratory, and imaging findings were assessed. Results: CAR T cells were administered intrapleurally in 31 patients (33 procedures, 2 patients were administered a second dose) with successful delivery of planned dose (10–186 mL); 14/33 (42%) intracavitary and 19/33 (58%) intratumoral. All procedures were completed within 2 h of T-cell thawing. There were no procedure-related adverse events greater than grade 1 (1 in 3 patients had prior ipsilateral pleural fusion procedures). The most common imaging finding was ground glass opacities with interlobular septal thickening and/or consolidation, observed in 12/33 (36%) procedures. There was no difference in the incidence of fever, CRP, IL-6, and peak vector copy number in the peripheral blood between infusion methods. Conclusion: Image-guided intrapleural delivery of CAR T cells using intracavitary or intratumoral routes is feasible, repeatable and safe across anatomically variable pleural cancers. © 2022 Elsevier B.V. |
| Keywords: | adoptive cell therapy; malignant pleural mesothelioma; malignant pleural effusion; regional delivery; pleural metastases |
| Journal Title: | Lung Cancer |
| Volume: | 165 |
| ISSN: | 0169-5002 |
| Publisher: | Elsevier Ireland Ltd. |
| Date Published: | 2022-03-01 |
| Start Page: | 1 |
| End Page: | 9 |
| Language: | English |
| DOI: | 10.1016/j.lungcan.2022.01.003 |
| PROVIDER: | scopus |
| PUBMED: | 35045358 |
| PMCID: | PMC9256852 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2022 -- Source: Scopus |
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