title: Phase II trial of a GM-CSF-producing and CD40L-expressing bystander cell line combined with an allogeneic tumor cell-based vaccine for refractory lung adenocarcinoma.
abstract: We created a vaccine in which irradiated allogeneic lung adenocarcinoma cells are combined with a bystander K562 cell line transfected with hCD40L and hGM-CSF. By recruiting and activating dendritic cells, we hypothesized that the vaccine would induce tumor regression in metastatic lung adenocarcinoma. Intradermal vaccine was given q14 days×3, followed by monthly ×3. Cyclophosphamide (300 mg/m IV) was administered before the first and fourth vaccines to deplete regulatory T cells. All-trans retinoic acid was given (150/mg/m/d) after the first and fourth vaccines to enhance dendritic cell differentiation. Twenty-four participants were accrued at a single institution from October 2006 to June 2008, with a median age 64 years and median of 4 previous lines of systemic therapy. A total of 101 vaccines were administered. Common toxicities were headache (54%) and site reaction (38%). No radiologic responses were observed. Median overall survival was 7.9 months and median progression-free survival was 1.7 months. Of 14 patients evaluable for immunological study, 5 had peptide-induced CD8 T-cell activation after vaccination. Overall, vaccine administration was feasible in an extensively pretreated population of metastatic lung cancer. Despite a suggestion of clinical activity in the subset with immune response, the trial did not meet the primary endpoint of inducing radiologic tumor regression.
authors.affiliation: *Department of Oncologic Sciences, University of South Florida †H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL ‡MD Anderson Cancer Center, Houston, TX §Karmanos Cancer Institute, Wayne State University, Detroit, MI.
authors.forename: Ben C
authors.initials: BC
authors.lastname: Creelan
authors.forename: Scott
authors.initials: S
authors.lastname: Antonia
authors.forename: David
authors.initials: D
authors.lastname: Noyes
authors.forename: Terri B
authors.initials: TB
authors.lastname: Hunter
authors.forename: George R
authors.initials: GR
authors.lastname: Simon
authors.forename: Gerold
authors.initials: G
authors.lastname: Bepler
authors.forename: Charles C
authors.initials: CC
authors.lastname: Williams
authors.forename: Tawee
authors.initials: T
authors.lastname: Tanvetyanon
authors.forename: Eric B
authors.initials: EB
authors.lastname: Haura
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schell
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiappori
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D000368:Aged; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology; D024201:Bystander Effect; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D008175:Lung Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012008:Recurrence; D016019:Survival Analysis; D019076:Transgenes / Q000235:genetics; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D023201:CD40 Ligand; D014212:Tretinoin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor