Human gene therapy for melanoma: CT-guided interstitial injection

William Waddill, William Wright, Evan Unger, Alison Stopeck, Emmanuel Akporiaye, David Harris, Thomas Grogan, Samuel Schluter, Evan Hersh, Susan Stahl

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

OBJECTIVE. Our intent is to describe the role of CT in the intratumoral injection of Allovectin-7 (Vical, San Diego, CA), an allogeneic class I major histocompatibility complex antigen, HLA-B7, formulated with cationic lipid, in the treatment of metastatic malignant melanoma. MATERIALS AND METHODS. Ten patients with metastatic malignant melanoma were treated with gene therapy in which we used CT-guided intratumoral injection of plasmid DNA containing the HLA-B7 gene. This therapy was part of a phase I gene therapy trial in patients with metastatic melanoma. CT guidance was chosen as an accurate way to direct gene delivery in patients with deep, impalpable lesions. Tumor locations included pulmonary, mediastinal, hepatic; adrenal, and paracaval sites. Patients in the CR protocol underwent baseline CT studies. Examinations were repeated 2, 4, and 8 weeks after gene therapy and thereafter at 3-month intervals. Both injected and noninjected tumors were measured. CT-guided injections of 10, 50, or 250 μg of plasmid DNA were performed with 22-gauge spinal needles. Injection volumes were between 1.0 and 4.0 ml, depending on tumor size. CT-guided core biopsy specimens were obtained (with 18- or 20-gauge needles) from the selected tumor before therapy and 2, 4, and 8 weeks after therapy to assess HLA-B7 plasmid DNA and gene expression. Peripheral blood was analyzed for cytotoxic T lymphocytes directed against HLA-B7. RESULTS. CT-guided intratumoral injections were successful in delivering genetic material to all patients with implantable tumors. Significant responses (as defined by a decrease of 25% or more in the product of the length and width of the injected tumor) were observed in six of the 10 patients. One of these six of the 10 patients. One of these six patients who had a solitary lesion remains free of disease 19 months after gene therapy. HLA-B7 protein expression was detected in 89% of biopsy specimens, and plasmid DNA and messenger RNA were detected in 56% and 22% of biopsy specimens, respectively. CONCLUSION. CT provides a safe, accurate, and efficacious way to monitor and assess tumor progression and response, and it provides guidance for biopsies and intratumoral injections during gene therapy. Significant responses in injected tumors of six of the 10 patients in our study suggest that further clinical trials of this gene therapy are warranted.

Original languageEnglish (US)
Pages (from-to)63-67
Number of pages5
JournalAmerican Journal of Roentgenology
Volume169
Issue number1
DOIs
StatePublished - Jul 1997

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'Human gene therapy for melanoma: CT-guided interstitial injection'. Together they form a unique fingerprint.

Cite this