Phase I Hepatic Immunotherapy for Metastases Study of Intra-Arterial Chimeric Antigen Receptor-Modified T-cell Therapy for CEA+ Liver Metastases.
Clin Cancer Res
; 21(14): 3149-59, 2015 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-25850950
ABSTRACT
PURPOSE:
Chimeric antigen receptor-modified T cells (CAR-T) have demonstrated encouraging results in early-phase clinical trials. Successful adaptation of CAR-T technology for CEA-expressing adenocarcinoma liver metastases, a major cause of death in patients with gastrointestinal cancers, has yet to be achieved. We sought to test intrahepatic delivery of anti-CEA CAR-T through percutaneous hepatic artery infusions (HAIs). EXPERIMENTALDESIGN:
We conducted a phase I trial to test HAI of CAR-T in patients with CEA(+) liver metastases. Six patients completed the protocol, and 3 received anti-CEA CAR-T HAIs alone in dose-escalation fashion (10(8), 10(9), and 10(10) cells). We treated an additional 3 patients with the maximum planned CAR-T HAI dose (10(10) cells × 3) along with systemic IL2 support.RESULTS:
Four patients had more than 10 liver metastases, and patients received a mean of 2.5 lines of conventional systemic therapy before enrollment. No patient suffered a grade 3 or 4 adverse event related to the CAR-T HAIs. One patient remains alive with stable disease at 23 months following CAR-T HAI, and 5 patients died of progressive disease. Among the patients in the cohort that received systemic IL2 support, CEA levels decreased 37% (range, 19%-48%) from baseline. Biopsies demonstrated an increase in liver metastasis necrosis or fibrosis in 4 of 6 patients. Elevated serum IFNγ levels correlated with IL2 administration and CEA decreases.CONCLUSIONS:
We have demonstrated the safety of anti-CEA CAR-T HAIs with encouraging signals of clinical activity in a heavily pretreated population with large tumor burdens. Further clinical testing of CAR-T HAIs for liver metastases is warranted.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quimioterapia do Câncer por Perfusão Regional
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Receptores de Antígenos de Linfócitos T
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Linfócitos T
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Adenocarcinoma
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Imunoterapia
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Neoplasias Hepáticas
Tipo de estudo:
Guideline
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2015
Tipo de documento:
Article