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Immunotherapy Task Force Meeting Report
With the Federal Drug Administration’s approval of Gardasil for prevention of cervical cancer, the interest in employing immunotherapeutic strategies for other types of cancers has been amplified, especially since there is a low incidence of significant toxicities. In patients with high-grade gliomas, multiple investigators have tested a variety of immunotherapeutic approaches that have recently demonstrated great promise (Table 1). Nonetheless, these studies need to be validated in phase III studies. Three studies are moving forward this fall as multicenter pharmaceutical trials (Table 2). The first, by Northwest Biotherapeutics, involves creating a patient-specific vaccine from the patient’s dendritic cells and tumor obtained at the time of surgery. The second one is a registration trial by Celldex Therapeutics that utilizes an “off-the-shelf” peptide that results in the immune targeting of the tumor-specific antigen, epidermal growth factor variant III. The last trial by Bradmer Pharmaceuticals consists of administration into surgically created cavities of a monoclonal antibody to the glioma specific target tenascin. Additional information and the names of participating sites can be obtained from their respective web sites, www.nwbio.com, www.celldextherapeutics.com, and www.bradmerpharma.com. General information on clinical trials can be obtained from http://virtualtrials.com. Efforts are also underway throughout Europe to conduct clinical trials utilizing dendritic cell immunotherapy for high grade malignant glioma patients.
Agent delivered/
Site |
Phase |
Sponsor or Centers Involved |
Results |
GM-CSF + PEP-3-KLH (ACTIVATE)/
Systemic |
II |
Duke University Medical Center/The Univ. of Texas M. D. Anderson Cancer Center |
Median survival = 2.4 years
(NOTE: newly diagnosed; n=23) |
Personalized peptide vaccines (4)/
Systemic |
I |
Nigata University |
Median survival = 1.7 years
(NOTE: recurrent GBM; n=17) |
Dendritic cells + PEP-3-KLH/
Systemic |
II |
Duke University Medical Center |
Median survival = 1.8 years
(NOTE: newly diagnosed; n=14) |
Dendritic cells + tumor lysate/acid-eluted peptides/
Systemic |
I, II |
Cedars Sinai Medical Center |
Median survival = 1.24 – 2.55 years
(NOTE: recurrent and newly diagnosed) |
Dendritic cells fused with glioma cells + IL-12/
Systemic |
I |
Institute of DNA Medicine
Tokyo Japan |
4/15 patients demonstrated 50% reduction in tumor size
(NOTE: mixed grades of gliomas) |
Whole cell vaccine with TGF-ß2 antisense/
Systemic |
I |
Advanced Biotherapies |
Median survival = 1.4 years for all; 1.6 years for patients responding immunologically (NOTE: progressing GBM patients at enrollment; n=6) |
Heat shock protein/
Systemic |
I |
Univ. of California at San Francisco |
Delay in time to progression compared with contemporaneous patients treated with chemotherapy |
Poly-ICLC/
Systemic |
II |
North American Brain Tumor Coalition |
Median survival = 1.6 years |
131I labeled Anti-tenascin monoclonal antibody
Intracavitary |
II |
Duke University Medical Center |
Median survival = 1.65 years
(NOTE: newly diagnosed GBM; n=27) |
Agent delivered/
Site
|
Phase |
Sponsor or Centers Involved |
Eligibility |
GM-CSF + PEP-3-KLH + temozolomide versus standard of care temozolomide/
Systemic |
II/III |
Celldex Therapeutics
20 National |
Newly diagnosed GBM, gross-total resection, EGFRvIII +, no progression post radiation |
131I-labeled antitenascin (Neuradiab)/
Intracavitary |
III |
Bradmer Pharaceuticals |
Newly diagnosed GBM,
gross total resection |
Dendritic cells + tumor lysate
(DCVax-Brain)/
Systemic |
II |
Northwestern Biotherapeutics |
Newly diagnosed GBM |
GM-CSF + PEP-3-KLH + temozolomide
(ACTIVATE II)/
Systemic |
II |
Duke University Medical Center/The Univ. of Texas M. D. Anderson Cancer Center |
Newly diagnosed GBM, gross-total resection, EGFRvIII +, no progression post radiation |
Heat Shock Protein (HSPPC-96)/
Systemic |
I |
Univ. of Calif. at San Francisco |
Recurrent high grade |
Dendritic cells + multiple peptides/
Systemic |
I/II |
University of Pittsburgh |
Recurrent GBM/AA, HLA-A2+ |
Poly-ICLC/
Systemic |
II |
North American Brain Tumor Coalition |
Anaplastic astrocytoma |
The investigational efforts in the fields of neuro-oncology immunology and immunotherapy have been prominently featured this year at the annual meetings of the American Association for Cancer Research, the American Association of Neurological Surgeons, the American Society of Clinical Oncology, the American Association of Immunologists, the Congress of Neurological Surgeons, and the Society for Neuro-Oncology. Recently concluded was the 3rd Annual Brain Tumor Immunotherapy Symposium at the Givens Institute in Aspen, Colorado, August 5-8, 2007. In previous years the Immunotherapy Task Force has met as a satellite Meeting along side the Society for Neuro-oncology Annual Meeting; however this year the formatting has been changed and will be included as a seminar session in Dallas, TX, November 15-18th. Brain Tumor Immunotherapy, an International Symposium hosted by the National Neurological Institute will be held in Milan, Italy on October 19, 2007.
As we move forward over the next year, we will begin to compile a database of investigators who are interested in conducting clinical trials in the field of immunotherapy that can be made available to pharmaceutical companies and consortium groups. If you wish to be added to the list of future contacts, please e-mail aheimber@mdanderson.org. |
