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A Phase I-II Study of α-Galactosylceramide-Pulsed IL-2/GM-CSF-Cultured Peripheral Blood Mononuclear Cells in Patients with Advanced and Recurrent Non-Small Cell Lung Cancer
- Source :
- The Journal of Immunology. 182:2492-2501
- Publication Year :
- 2009
- Publisher :
- The American Association of Immunologists, 2009.
-
Abstract
- To evaluate the safety, immune responses, and antitumor responses after the administration of α-galactosylceramide (αGalCer) KRN7000-pulsed PBMC cultured with IL-2 and GM-CSF (IL-2/GM-CSF-cultured PBMCs), a phase I-II study in patients with non-small cell lung cancer was conducted. Patients with advanced non-small cell lung cancer or recurrent lung cancer refractory to the standard therapy were eligible. αGalCer-pulsed IL-2/GM-CSF-cultured PBMCs (1 × 109/m2) were i.v. administered four times. Immune responses were monitored weekly. Twenty-three patients were enrolled in this study and 17 cases (73.9%) completed. No severe adverse event related to the treatment was observed. After the injection of αGalCer-pulsed IL-2/GM-CSF-cultured PBMCs, an increased number of IFN-γ-producing cells in the peripheral blood were detected in 10 patients (58.8%). Five cases remained as stable disease, and the remaining 12 cases were evaluated as progressive disease. The estimated median survival time (MST) of the 17 cases was 18.6 mo (range, 3.8 to 36.3 mo). Ten patients who displayed increased IFN-γ-producing cells (≥2-fold) showed prolonged MST (31.9 mo; range, 14.5 to 36.3 mo) as compared with poor-responder patients (n = 7) MST (9.7 mo; range, 3.8 to 25.0 mo) (log-rank test, p = 0.0015). The administration of αGalCer-pulsed IL-2/GM-CSF-cultured PBMCs was well tolerated and was accompanied by the successful induction of NKT cell-dependent immune responses. The increased IFN-γ-producing cells that result from αGalCer stimulation in PBMCs were significantly associated with prolonged MST. These results are encouraging and warrant further evaluation for survival benefit of this immunotherapy.
- Subjects :
- Adult
Male
Interleukin 2
Lung Neoplasms
medicine.medical_treatment
Immunology
Galactosylceramides
Kaplan-Meier Estimate
Cancer Vaccines
Immunotherapy, Adoptive
Peripheral blood mononuclear cell
Interferon-gamma
Immune system
Carcinoma, Non-Small-Cell Lung
Carcinoma
medicine
Humans
Immunology and Allergy
Cells, Cultured
Aged
business.industry
Granulocyte-Macrophage Colony-Stimulating Factor
Immunotherapy
Middle Aged
Flow Cytometry
medicine.disease
Natural killer T cell
Granulocyte macrophage colony-stimulating factor
Leukocytes, Mononuclear
Interleukin-2
Natural Killer T-Cells
Female
Neoplasm Recurrence, Local
business
Progressive disease
medicine.drug
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 182
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....b5435243339e33684299e9c5db281a63