Journal
JOURNAL OF IMMUNOLOGY
Volume 182, Issue 4, Pages 2492-2501Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0800126
Keywords
-
Categories
Funding
- Japan's Ministry of Education, Culture. Sports, Science and Technology (MEXT) [17016010, 17390139, 19591609]
- Exploratory Research [19659121]
- Cancer Translational Research Project
- Ministry of Health, Labor and Welfare (Japan)
- Japan Health Science Foundation
- Yasuda Medical Foundation
- Sagawa Foundation
- Kobayashi Institute for Innovative Cancer Chemotherapy
- Grants-in-Aid for Scientific Research [21591808, 17390139, 19659121, 19591609] Funding Source: KAKEN
Ask authors/readers for more resources
To evaluate the safety, immune responses, and antitumor responses after the administration of a-galactosylceramide (alpha GalCer) 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. alpha GalCer-pulsed IL-2/GM-CSF-cultured PBMCs (I X 10(9)/m(2)) 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 aGalCer-pulsed IL-2/GM-CSF-cultured PBMCs, an increased number of IFN-gamma-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-gamma-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 aGalCer-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-gamma-producing cells that result from aGalCer stimulation in PBMCs were significantly associated with prolonged MST. These results are encouraging and warrant further evaluation for survival benefit of this immunotherapy. The Journal of Immunology, 2009, 182: 2492-2501.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available