Direct gene transfer with DNA-liposome complexes in melanoma: Expression, biologic activity, and lack of toxicity in humans

Gary J. Nabel, Elizabeth G. Nabel, Zhi Yong Yang, Bernard A. Fox, Gregory E. Plautz, Xiang Gao, Leaf Huang, Suyu Shu, David Gordon, Alfred E. Chang

Research output: Contribution to journalArticlepeer-review

857 Scopus citations


Direct gene transfer offers the potential to introduce DNA encoding therapeutic proteins to treat human disease. Previously, gene transfer in humans has been achieved by a cell-mediated ex vivo approach in which cells from the blood or tissue of patients are genetically modified in the laboratory and subsequently returned to the patient. To determine the feasibility and safety of directly transferring genes into humans, a clinical study was performed. The gene encoding a foreign major histocompatibility complex protein, HLA-B7, was introduced into HLA-B7-negative patients with advanced melanoma by injection of DNA-liposome complexes in an effort to demonstrate gene transfer, document recombinant gene expression, and determine the safety and potential toxicity of this therapy. Six courses of treatment were completed without complications in five HLA-B7-negative patients with stage IV melanoma. Plasmid DNA was detected within biopsies of treated tumor nodules 3-7 days after injection but was not found in the serum at any time by using the polymerase chain reaction. Recombinant HLA-B7 protein was demonstrated in tumor biopsy tissue in all five patients by immunochemistry, and immune responses to HLA-B7 and autologous tumors could be detected. No antibodies to DNA were detected in any patient. One patient demonstrated regression of injected nodules on two independent treatments, which was accompanied by regression at distant sites. These studies demonstrate the feasibility, safety, and therapeutic potential of direct gene transfer in humans.

Original languageEnglish (US)
Pages (from-to)11307-11311
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - Dec 1 1993
Externally publishedYes


  • Gene therapy
  • Human clinical trials
  • Immunotherapy
  • Major histocompatibility complex

ASJC Scopus subject areas

  • General
  • Genetics


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