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Phase I study of direct gene transfer of an allogeneic histocompatibility antigen, HLA-B7, in patients with metastatic melanoma.

AbstractPURPOSE:
To determine the safety, toxicity, and efficacy of direct intratumoral injection of an allogeneic major histocompatibility complex (MHC) class I gene, HLA-B7, in a cationic lipid vector (Allovectin-7; Vical Inc, San Diego, CA) in patients with metastatic melanoma.
PATIENTS AND METHODS:
Seventeen HLA-B7-negative patients were treated with intralesional injection of Allovectin-7. Twelve patients received a single intralesional injection containing 10 micrograms (four patients), 50 micrograms (five patients), or 250 micrograms (three patients) of plasmid DNA. Five patients received two or three injections of 10 micrograms DNA to a single tumor site at 2-week intervals. Tumor biopsies pretherapy and 2 and 4 weeks after gene injection were obtained to determine expression of the plasmid by polymerase chain reaction (PCR), reverse transcriptase (RT)-PCR, flow cytometry, and immunohistochemistry.
RESULTS:
Toxicities were related to technical aspects of the injections or biopsies. These included pain, hemorrhage, pneumothorax, and hypotension. Two patients were hospitalized overnight for observation. Seven patients (50%) had tumor responses insofar as the injected nodule decreased > or = 25% by radiologic or physical examination. One patient with a single site of disease achieved a complete remission. Ninety-three percent of the patients' post-gene therapy biopsies contained HLA-B7 plasmid DNA, mRNA, or protein.
CONCLUSION:
Intratumoral injection of the allogeneic histocompatibility gene, HLA-B7, in a lipid vector can be performed safely at plasmid DNA doses < or = 250 micrograms. The safety profile and biologic activity of this therapy warrants further studies to define the mechanism of action, predictors of response, and antitumor efficacy of this approach.
AuthorsA T Stopeck, E M Hersh, E T Akporiaye, D T Harris, T Grogan, E Unger, J Warneke, S F Schluter, S Stahl
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 15 Issue 1 Pg. 341-9 (Jan 1997) ISSN: 0732-183X [Print] United States
PMID8996161 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Allovectin-7
  • DNA, Recombinant
  • HLA-B7 Antigen
  • Lipids
  • DNA
Topics
  • Adult
  • Aged
  • DNA
  • DNA, Recombinant
  • Feasibility Studies
  • Female
  • Flow Cytometry
  • Gene Transfer Techniques (adverse effects)
  • HLA-B7 Antigen (administration & dosage, adverse effects, genetics, immunology)
  • Humans
  • Immunohistochemistry
  • Injections, Intralesional
  • Lipids (administration & dosage, adverse effects, genetics)
  • Male
  • Melanoma (immunology, secondary, therapy)
  • Middle Aged
  • Plasmids (administration & dosage, adverse effects, genetics)
  • Polymerase Chain Reaction (methods)

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