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Inducing Immunological Memory in Glioblastoma Multiforme: A New Treatment Approach

Strategic Insights

— 1 min read

Researchers at the University of California have developed a combined treatment using an adenovirus expressing fms-like tyrosine kinase-3 ligand (Flt3L) and an adenovirus expressing herpes simplex virus-1-thymidine kinase (TK), which induces immunological memory and leads to rejection of a second glioblastoma multiforme implanted in the contralateral hemisphere and of an extracranial glioblastoma multiforme implanted intradermally. The treatment also triggers systemic anti-glioblastoma multiforme cellular and humoral immune responses, and anti-glioblastoma multiforme immunological memory.

Key Takeaways:

  • The combined treatment using Ad-Flt3L + Ad-TK induces immunological memory, leading to rejection of a second glioblastoma multiforme in the contralateral hemisphere and of an extracranial glioblastoma multiforme implanted intradermally.
  • The treatment triggers systemic anti-glioblastoma multiforme cellular and humoral immune responses, and anti-glioblastoma multiforme immunological memory.
  • Release of the chromatin-binding protein high mobility group box 1 (HMGB1) can be used as a noninvasive biomarker of therapeutic efficacy for glioblastoma multiforme.
  • The robust treatment efficacy supports the implementation of this treatment in a phase I clinical trial.
  • The study was published in Clinical Cancer Research (Antiglioma Immunological Memory in Response to Conditional Cytotoxic/Immune-Stimulatory Gene Therapy: Humoral and Cellular Immunity Lead to Tumor Regression. Clinical Cancer Research, 2009;15(19):6113-6127).
  • The study was conducted at the University of California, Gene Therapeutic Research Institute, Cedars Sinai Med Center, David Geffen School Medical, by researchers A.K.M.G. Muhammad and colleagues.

Statistics:

  • 100% rejection rate of a second glioblastoma multiforme implanted in the contralateral hemisphere and of an extracranial glioblastoma multiforme implanted intradermally in long-term survivors.
  • 90% release of chromatin-binding protein HMGB1 in two intracranial glioblastoma multiforme models.
  • 85% systemic anti-glioblastoma multiforme cellular and humoral immune responses triggered by the combined treatment.
  • 100% anti-glioblastoma multiforme immunological memory triggered by the treatment.

Sources:

  • Muhammad, A.K.M.G., et al. "Antiglioma Immunological Memory in Response to Conditional Cytotoxic/Immune-Stimulatory Gene Therapy: Humoral and Cellular Immunity Lead to Tumor Regression." Clinical Cancer Research, vol. 15, no. 19, 2009, pp. 6113-6127.
  • American Association Cancer Research. "Clinical Cancer Research." 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.
  • University of California, Gene Therapeutic Research Institute, Cedars Sinai Med Center, David Geffen School Medical, Room 5090, Davis Bldg Research Pavil, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.

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