title: Summary of bi-shRNA/GM-CSF augmented autologous tumor cell immunotherapy (FANG™) in advanced cancer of the liver.
abstract: Therapies for advanced hepatocellular carcinoma (HCC) are limited. We carried out a phase I trial of a novel autologous whole-cell tumor cell immunotherapy (FANG™), which incorporates a dual granulocyte macrophage colony-stimulating factor (GM-CSF) expressive/bifunctional small hairpin RNA interference (bi-shRNAi) vector. The bi-shRNAi DNA targets furin, which is a proconvertase of transforming growth factors beta (TGFβ) 1 and 2. Safety, mechanism, immunoeffectiveness, and suggested benefit were previously shown [Senzer et al.: Mol Ther 2012;20:679-689; Senzer et al.: J Vaccines Vaccin 2013;4:209]. We now provide further follow-up of a subset of 8 HCC patients. FANG manufacturing was successful in 7 of 8 attempts (one failure due to insufficient cell yield). Median GM-CSF expression was 144 pg/10(6) cells, TGFβ1 knockdown was 100%, and TGFβ2 knockdown was 93% of the vector-transported cells. Five patients were vaccinated (1 or 2.5×10(7) cells/intradermal injection, 6-11 vaccinations). No FANG toxicity was observed. Three of these patients demonstrated evidence of an immune response to the autologous tumor cell sample. Long-term follow-up demonstrated survival of 319, 729, 784, 931+, and 1,043+ days of the FANG-treated patients. In conclusion, evidence supports further assessment of the FANG immunotherapy in HCC.
authors: Mary Crowley Cancer Research Centers, Dallas, Tex., USA.
authors: John
authors: J
authors: Nemunaitis
authors: Minal
authors: M
authors: Barve
authors: Douglas
authors: D
authors: Orr
authors: Joseph
authors: J
authors: Kuhn
authors: Mitchell
authors: M
authors: Magee
authors: Jeffrey
authors: J
authors: Lamont
authors: Cynthia
authors: C
authors: Bedell
authors: Gladice
authors: G
authors: Wallraven
authors: Beena O
authors: BO
authors: Pappen
authors: Alyssa
authors: A
authors: Roth
authors: Staci
authors: S
authors: Horvath
authors: Derek
authors: D
authors: Nemunaitis
authors: Padmasini
authors: P
authors: Kumar
authors: Phillip B
authors: PB
authors: Maples
authors: Neil
authors: N
authors: Senzer
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007271:Injections, Intradermal; D008113:Liver Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000235:genetics*; D016019:Survival Analysis; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D034741:RNA, Small Interfering; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor