RT Journal Article
SR Electronic
T1 A pilot study of an autologous tumor-derived autophagosome vaccine with docetaxel in patients with stage IV non-small cell lung cancer
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP 103
DO 10.1186/s40425-017-0306-6
VO 5
IS 1
A1 Rachel E. Sanborn
A1 Helen J. Ross
A1 Sandra Aung
A1 Anupama Acheson
A1 Tarsem Moudgil
A1 Sachin Puri
A1 Traci Hilton
A1 Brenda Fisher
A1 Todd Coffey
A1 Christopher Paustian
A1 Michael Neuberger
A1 Edwin Walker
A1 Hong-Ming Hu
A1 Walter J. Urba
A1 Bernard A. Fox
YR 2017
UL http://jitc.bmj.com/content/5/1/103.abstract
AB Background Tumor-derived autophagosome vaccines (DRibbles) have the potential to broaden immune response to poorly immunogenic tumors.Methods Autologous vaccine generated from tumor cells harvested from pleural effusions was administered to patients with advanced NSCLC with the objectives of assessing safety and immune response. Four patients were vaccinated and evaluable for immune response; each received two to four doses of vaccine. Study therapy included two cycles of docetaxel 75 mg/m2 on days 1 and 29 to treat the tumor, release hidden antigens and produce lymphopenia. DRibbles were to be administered intradermally on days 14, 43, 57, 71, and 85, together with GM-CSF (50 μg/d x 6d, administered via SQ mini pump). Peripheral blood was tested for immune parameters at baseline and at each vaccination.Results Three of four patients had tumor cells available for testing. Autologous tumor-specific immune response was seen in two of the three, manifested by IL-5 (1 patient after 3 doses), and IFN-γ, TNF-α, IL-5, IL-10 (after 4 doses in one patient). All 4 patients had evidence of specific antibody responses against potential tumor antigens. All patients came off study after 4 or fewer vaccine treatments due to progression of disease. No significant immune toxicities were seen during the course of the study.Conclusions DRibble vaccine given with GM-CSF appeared safe and capable of inducing an immune response against tumor cells in this small, pilot study. There was no evidence of efficacy in this small poor-prognosis patient population, with treatment not feasible. Trial registration NCT00850785, initial registration date February 23, 2009.Abbreviations:BDBecton DickinsonCTCAECommon Terminology Criteria for Adverse EventsDAMPsDamage-associated molecular pattern moleculesDRibblesDRiPs in blebsDRiPsDefective ribosomal productsECOGEastern Cooperative Oncology GroupFITCFluorescein isothiocyanateGM-CSFGranulocyte-Monocyte colony stimulating factorGPM6AGlycoprotein M6AHRPHorseradish peroxidaseNSCLCNon-small cell lung cancerPBMCPeripheral blood mononuclear cellsPD-1Programmed cell death receptor-1RPS6KP1Ribosomal protein S6 kinase polypeptide 1RRAGBRas-related GTP binding BSLiPsShort-lived proteins