title: Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer.
abstract: OBJECTIVE
  Belagenpumatucel-L is a nonviral gene-based allogeneic tumor cell vaccine that demonstrates enhancement of tumor antigen recognition as a result of transforming growth factor beta-2 inhibition.
  
  
  METHODS
  We performed a randomized, dose-variable, phase II trial involving stages II, IIIA, IIIB, and IV non-small-cell lung cancer patients. Each patient received one of three doses (1.25, 2.5, or 5.0 x 10(7) cells/injection) of belagenpumatucel-L on a monthly or every other month schedule to a maximum of 16 injections. Immune function, safety, and anticancer activity were monitored.
  
  
  RESULTS
  Seventy-five patients (two stage II, 12 stage IIIA, 15 stage IIIB, and 46 stage IV patients) received a total of 550 vaccinations. No significant adverse events were observed. A dose-related survival difference was demonstrated in patients who received > or = 2.5 x 10(7) cells/injection (P = .0069). Focusing on the 61 late-stage (IIIB and IV) assessable patients, a 15% partial response rate was achieved. The estimated probabilities of surviving 1 and 2 years were 68% and 52%, respectively for the higher dose groups combined and 39% and 20%, respectively, for the low-dose group. Immune function was explored in the 61 advanced-stage (IIIB and IV) patients. Increased cytokine production (at week 12 compared with patients with progressive disease) was observed among clinical responders (interferon gamma, P = .006; interleukin [IL] -6, P = .004; IL-4, P = .007), who also displayed an elevated antibody-mediated response to vaccine HLAs (P = .014). Furthermore, positive enzyme-linked immunospot reactions to belagenpumatucel-L showed a correlation trend (P = .086) with clinical responsiveness in patients achieving stable disease or better.
  
  
  CONCLUSIONS
  Belagenpumatucel-L is well tolerated, and the survival advantage justifies further phase III evaluation.
authors.affiliation: Mary Crowley Medical Research Center/Texas Oncology Professional Association, Dallas, TX, USA. jnemunaitis@mcmrc.com
authors.forename: John
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: Robert O
authors.initials: RO
authors.lastname: Dillman
authors.forename: Paul O
authors.initials: PO
authors.lastname: Schwarzenberger
authors.forename: Neil
authors.initials: N
authors.lastname: Senzer
authors.forename: Casey
authors.initials: C
authors.lastname: Cunningham
authors.forename: Jodi
authors.initials: J
authors.lastname: Cutler
authors.forename: Alex
authors.initials: A
authors.lastname: Tong
authors.forename: Padmasini
authors.initials: P
authors.lastname: Kumar
authors.forename: Beena
authors.initials: B
authors.lastname: Pappen
authors.forename: Cody
authors.initials: C
authors.lastname: Hamilton
authors.forename: Edward
authors.initials: E
authors.lastname: DeVol
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Maples
authors.forename: Lily
authors.initials: L
authors.lastname: Liu
authors.forename: Terry
authors.initials: T
authors.lastname: Chamberlin
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Shawler
authors.forename: Habib
authors.initials: H
authors.lastname: Fakhrai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation / Q000187:drug effects; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016376:Oligonucleotides, Antisense / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D016019:Survival Analysis; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D053781:Transforming Growth Factor beta2; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D016376:Oligonucleotides, Antisense; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; C514428:belagenpumatucel L; D007371:Interferon-gamma