title: Intratumoral administration of a 1,2-dimyristyloxypropyl-3- dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine formulation of the human interleukin-2 gene in the treatment of metastatic renal cell carcinoma.
abstract: BACKGROUND
  Leuvectin (Vical Inc., San Diego, CA) is a gene transfer product in which a plasmid encoding the human interleukin-2 (IL-2) gene is complexed with the cationic lipid 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine (DMRIE/DOPE). In the current study, the authors investigated the safety and efficacy of in situ vaccination with Leuvectin in patients with metastatic renal cell carcinoma.
  
  
  METHODS
  Thirty-one patients with metastatic renal cell carcinoma were treated with intratumorally administered Leuvectin at doses ranging from 0.75 to 4 mg. These patients subsequently were evaluated for response and for treatment-related toxicity.
  
  
  RESULTS
  Treatment was well tolerated: no Grade 3 or 4 toxicities were observed in association with the study agent. Documented side effects included Grade 1 pain at the injection site (20%); mild (i.e., Grade 1 or 2) constitutional symptoms, including malaise/myalgia, low-grade fever, and chills (74%); Grade 1 fatigue (19%); Grade 1 or 2 nausea (10%); and Grade 2 allergy (1 occurrence). Two patients experienced partial responses, which endured for 32 months and 6 years, respectively, and 1 patient currently is experiencing a pathologic complete response, which, to date, has persisted for 50 months; thus, the overall response rate was 10%. In addition, 7 patients (23%) experienced disease stabilization for a median of 8 months (range, 4-48 months). The median duration of survival from the start of Leuvectin treatment was 11 months (range, 2-72 months), with a 1-year survival rate of 48% and a 3-year survival rate of 19%. Laboratory analysis of tumor samples revealed the presence of IL-2 plasmid DNA in six of eight patients posttreatment, increased IL-2 expression in tumor cells in four of eight patients posttreatment, and increased tumor infiltration by CD8-positive lymphocytes in five of eight patients posttreatment.
  
  
  CONCLUSIONS
  Immunotherapy with intratumorally administered Leuvectin is safe and can lead to durable objective responses in patients with metastatic renal cell carcinoma.
authors.affiliation: Department of Oncology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA. galanis.evanthia@mayo.edu
authors.forename: Evanthia
authors.initials: E
authors.lastname: Galanis
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Burch
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Richardson
authors.forename: Bradley
authors.initials: B
authors.lastname: Lewis
authors.forename: Henry C
authors.initials: HC
authors.lastname: Pitot
authors.forename: Stephen
authors.initials: S
authors.lastname: Frytak
authors.forename: Catherine
authors.initials: C
authors.lastname: Spier
authors.forename: Emmanuel T
authors.initials: ET
authors.lastname: Akporiaye
authors.forename: Prema P
authors.initials: PP
authors.lastname: Peethambaram
authors.forename: Judith S
authors.initials: JS
authors.lastname: Kaur
authors.forename: Scott H
authors.initials: SH
authors.lastname: Okuno
authors.forename: Krishnan K
authors.initials: KK
authors.lastname: Unni
authors.forename: Joseph
authors.initials: J
authors.lastname: Rubin
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D005260:Female; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics* / Q000276:immunology* / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D008055:Lipids / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010714:Phosphatidylethanolamines / Q000008:administration & dosage; D010957:Plasmids; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage; D016019:Survival Analysis
chemical_list: D019496:Cancer Vaccines; D007376:Interleukin-2; C494381:Leuvectin; D008055:Lipids; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; C087276:(3-dimyristyloxypropyl)(dimethyl)(hydroxyethyl)ammonium; C094877:dioleoyl phosphatidylethanolamine