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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Oncología > Inmunoterapia > DA - CIMA - Oncología - Inmunoterapia - Artículos de Revista >

Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas.
Authors: Mazzolini, G. (Guillermo)
Alfaro, C. (Carlos)
Sangro, B. (Bruno)
Feijoo, E. (Esperanza)
Ruiz, J. (Juan)
Benito, A. (Alberto)
Tirapu, I. (Íñigo)
Arina, A. (Ainhoa)
Sola, J. (Josu)
Herraiz-Bayod, M.J. (Maite J.)
Lucena, F. (Felipe)
Olagüe, C. (Cristina)
Subtil, J.C. (José Carlos)
Quiroga, J. (Jorge)
Herrero, J.I. (José Ignacio)
Sadaba, B. (Belén)
Bendandi, M. (Maurizio)
Qian, C. (Cheng)
Prieto, J. (Jesús)
Melero, I. (Ignacio)
Keywords: Dendritic Cells/immunology
Gastrointestinal Neoplasms/therapy
Interleukin-12/secretion
Killer Cells, Natural/immunology
Recombinant Proteins
Issue Date: 2005
Publisher: American Society of Clinical Oncology
Publisher version: http://jco.ascopubs.org/content/23/5/999
ISSN: 1527-7755
Citation: Mazzolini G, Alfaro C, Sangro B, Feijoo E, Ruiz J, Benito A, et al. Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas. J Clin Oncol 2005 Feb 10;23(5):999-1010.
Abstract
PURPOSE: To evaluate the feasibility and safety of intratumoral injection of autologous dendritic cells (DCs) transfected with an adenovirus encoding interleukin-12 genes (AFIL-12) for patients with metastatic gastrointestinal carcinomas. Secondarily, we have evaluated biologic effects and antitumoral activity. PATIENTS AND METHODS: Seventeen patients with metastatic pancreatic (n = 3), colorectal (n = 5), or primary liver (n = 9) malignancies entered the study. DCs were generated from CD14+ monocytes from leukapheresis, cultured and transfected with AFIL-12 before administration. Doses from 10 x 10(6) to 50 x 10(6) cells were escalated in three cohorts of patients. Patients received up to three doses at 21-day intervals. RESULTS: Fifteen (88%) and 11 of 17 (65%) patients were assessable for toxicity and response, respectively. Intratumoral DC injections were mainly guided by ultrasound. Treatment was well tolerated. The most common side effects were lymphopenia, fever, and malaise. Interferon gamma and interleukin-6 serum concentrations were increased in 15 patients after each treatment, as well as peripheral blood natural killer activity in five patients. DC transfected with AFIL-12 stimulated a potent antibody response against adenoviral capsides. DC treatment induced a marked increase of infiltrating CD8+ T lymphocytes in three of 11 tumor biopsies analyzed. A partial response was observed in one patient with pancreatic carcinoma. Stable disease was observed in two patients and progression in eight patients, with two of the cases fast-progressing during treatment. CONCLUSION: Intratumoral injection of DC transfected with an adenovirus encoding interleukin-12 to patients with metastatic gastrointestinal malignancies is feasible and well tolerated. Further studies are necessary to define and increase clinical efficacy.
Permanent link: http://hdl.handle.net/10171/18727
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Oncología - Inmunoterapia - Artículos de Revista
DA - CUN - Hematología y Hemoterapia - Artículos de revista
DA - CUN - Área de Terapia Celular - Artículos de revista
DA - Medicina - Hematología - Artículos de revista

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