Technical hurdles in a pilot clinical trial of combined B7-2 and GM-CSF immunogene therapy for glioblastomas and melanomas

Ian F Parney, Lung Ji Chang, Maxine A. Farr-Jones, Chunhai Hao, Michael Smylie, Kenneth C. Petruk

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Objective: Malignant glioblastomas and melanomas continue to have a dismal prognosis despite advances in conventional therapy. This has led to investigations of novel treatment strategies including immunogene therapy. We report a pilot clinical trial of combined B7-2 and GM-CSF immunogene therapy for gliomas and melanomas and discuss technical hurdles encountered. Methods: Patients with recurrent malignant gliomas or medically refractory melanomas were vaccinated with irradiated autologous tumor cells transduced with B7-2 and GM-CSF genes using a retroviral vector. Patients were monitored for toxicity, inflammatory/immune reactions, and clinical status. Results: Vaccine preparation was attempted from 116 malignant glioma and 32 melanoma specimens. Adequate vaccines could only be prepared for five glioblastoma and three melanoma patients. Six patients (three recurrent glioblastomas and three melanomas) were actually vaccinated. Minor toxicities included flu-like symptoms (3/6), injection site erythema (4/6), and asymptomatic elevations in liver enzymes (3/6). Most patients showed evidence of an inflammatory response but specific anti-tumor immunity was not demonstrated. All six patients have died, although three patients with minimal residual disease at treatment had prolonged recurrence-free intervals after vaccination. Conclusions: Combined B7-2 and GM-CSF immunogene therapy for glioblastomas and melanomas using autologous tumor cells has many technical pitfalls hindering large scale application and evaluation. As a result, this pilot study was too limited to draw meaningful conclusions regarding safety or anti-tumor immunity. While immunotherapy has been promising in pre-clinical studies, alternate strategies will be required to bring these benefits to patients.

Original languageEnglish (US)
Pages (from-to)71-80
Number of pages10
JournalJournal of Neuro-Oncology
Volume78
Issue number1
DOIs
StatePublished - May 2006
Externally publishedYes

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Glioblastoma
Granulocyte-Macrophage Colony-Stimulating Factor
Melanoma
Clinical Trials
Glioma
Therapeutics
Immunity
Neoplasms
Vaccines
Residual Neoplasm
Erythema
Immunotherapy
Vaccination
Safety
Recurrence
Injections
Liver
Enzymes
Genes

Keywords

  • Costimulation
  • Cytokine
  • Gene therapy
  • Glioblastoma
  • Immunotherapy
  • Melanoma

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neuroscience(all)

Cite this

Technical hurdles in a pilot clinical trial of combined B7-2 and GM-CSF immunogene therapy for glioblastomas and melanomas. / Parney, Ian F; Chang, Lung Ji; Farr-Jones, Maxine A.; Hao, Chunhai; Smylie, Michael; Petruk, Kenneth C.

In: Journal of Neuro-Oncology, Vol. 78, No. 1, 05.2006, p. 71-80.

Research output: Contribution to journalArticle

Parney, Ian F ; Chang, Lung Ji ; Farr-Jones, Maxine A. ; Hao, Chunhai ; Smylie, Michael ; Petruk, Kenneth C. / Technical hurdles in a pilot clinical trial of combined B7-2 and GM-CSF immunogene therapy for glioblastomas and melanomas. In: Journal of Neuro-Oncology. 2006 ; Vol. 78, No. 1. pp. 71-80.
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