title: Phase I/II trial of gene therapy with autologous tumor cells modified with tag7/PGRP-S gene in patients with disseminated solid tumors: miscellaneous tumors.
abstract: BACKGROUND
  The use of genetically modified autologous tumor cells appears to be a promising approach for cancer therapy. A phase I/II trial was undertaken to define the feasibility, safety and antitumor effects of the autologous vaccine prepared by transferring tag7/PGRP-S gene into malignant melanoma and renal cell carcinoma cells.
  
  
  METHODS
  Twenty-one patients (17 with disseminated malignant melanoma and four with metastatic renal cell carcinoma) were enrolled in this study. Cytoreduction was performed in all cases prior to therapy. Autologous tumor cells were transfected with the tag7/PGRP-S gene, irradiated and injected intradermally every 3 weeks.
  
  
  RESULTS
  Vaccinations were well tolerated by all patients, without clinically significant signs of toxicity. Delayed-type hypersensitivity was observed in 48% of cases. Antitumor immune response was observed in 95% of patients. There were no complete or partial responses; however, a minor response was achieved in one patient with renal cell carcinoma. The stabilization of neoplastic disease was observed in eight patients (seven with malignant melanoma and one with renal cell carcinoma). Median time to tumor progression was 3 months.
  
  
  CONCLUSIONS
  The approach suggested here appears to be well tolerated and produces a number of durable clinical effects. Further studies are required to determine whether promising effects on immune activation will result in an actual clinical benefit for patients with malignant melanoma and renal cell carcinoma.
authors.affiliation: N.N. Petrov Research Institute of Oncology, St Petersburg, Russian Federation.
authors.forename: V M
authors.initials: VM
authors.lastname: Moiseyenko
authors.forename: A O
authors.initials: AO
authors.lastname: Danilov
authors.forename: I A
authors.initials: IA
authors.lastname: Baldueva
authors.forename: A B
authors.initials: AB
authors.lastname: Danilova
authors.forename: N V
authors.initials: NV
authors.lastname: Tyukavina
authors.forename: S S
authors.initials: SS
authors.lastname: Larin
authors.forename: S L
authors.initials: SL
authors.lastname: Kiselev
authors.forename: R V
authors.initials: RV
authors.lastname: Orlova
authors.forename: V V
authors.initials: VV
authors.lastname: Anisimov
authors.forename: A I
authors.initials: AI
authors.lastname: Semenova
authors.forename: L A
authors.initials: LA
authors.lastname: Shchekina
authors.forename: G I
authors.initials: GI
authors.lastname: Gafton
authors.forename: V A
authors.initials: VA
authors.lastname: Kochnev
authors.forename: A S
authors.initials: AS
authors.lastname: Barchuk
authors.forename: S V
authors.initials: SV
authors.lastname: Kanaev
authors.forename: K P
authors.initials: KP
authors.lastname: Hanson
authors.forename: G P
authors.initials: GP
authors.lastname: Georgiev
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000628:therapy*; D016207:Cytokines / Q000235:genetics* / Q000627:therapeutic use*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000628:therapy*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000235:genetics* / Q000628:therapy*; D014162:Transfection; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; C491878:PGLYRP1 protein, human