Most significant of GBM is early diagnosis. An under trial personalized vaccine, HSPPA-96 is showing promise by extending life expectancy for median 8 to 12 months. Presently Avastin/ bevacizumab alone or with irinotecan is the standard treatment option for reccuring glioma and the other one is radiation therapy followed by surgery. Chemotherapeutics like Temozolomide, carmustine, O-6-benzylguanine, along with radiation showed better results. Other treatment options with Cisplatin, gefitinib,and erlotinib also are considered. Northwestern Medicine researchers are conducting trials on the efficacy of combined treatment of HSPPA-96 (personalized vaccine) along with standard Bevacizumab to treat GBM or atleast to increase the median life expectancy. This personalized vaccine showed new ways of finding targeted molecules to control cancers or recurring cancers. I think there is lot of scope studying GBM to find new treatment options for the people who are looking at scientists with a hope of not dying due to GBM... Early disease diagnosis Biomarker discovery holds promise in finding targets to kill or stop spreading tentacles of GBM, which may lead to targeted therapy....

Restricting my attention to seminal clinical trials with clear statement of survival outcome as endpoint, we have the Duke/MD Anderson Phase II ACTIVATE Trial [1] of the EGFRvIII-targeted peptide-based vaccine PEP-3-KLH (under the experimental drug name Rindopepimut; see below), plus growth support (GM-CSF) yielded a median survival of 2.4 years, while the same sponsors conducted another Phase II trial of this same regimen (PEP-3-KLH + GM-CSF) [2] but with temozolomide (TMZ) added which however failed to offer a survival advantage (median survival = 1.9 years).

Duke University Medical center (DUMC) also conducted an earlier Phase I/II GBM trial, reported at ASCO 2010 [3], using another epidermal growth factor receptor variant III (EGFRvIII)-targeted vaccine, DCs + PEP-3-KLH, which included a dendritic cell base, with median survival time = 1.8 years, along with another Phase II trial of a dendritic cell-based vaccine targeting CMV (cytomegalovirus) [4] that yielded median survival time exceeding 1.6 years (final median OS not yet reached). All these trials were in newly diagnosed GBM patients.

A number of other trials used DC-(dendritic cell) based immunotherapies in GBM. A Cedars Sinai Medical Center Phase I/II trial [5] deployed DCs + acid-eluted tumor peptides, yielding a modest median survival time of 1.3 years (newly diagnosed GBM), while another Cedars Sinai Phase II trial [6] used a DC-based vaccine plus tumor homogenate to yield in immune responders 1.8 years median survival (newly diagnosed) and 1.6 years (recurrent GBM). And the DCs + acid-eluted tumor peptides approach was again taken (as in the first Cedars Sinai trial) in a UCLA Phase I trial [7] which yielded median survival time = 2.0 years (newly diagnosed, and recurrent, GBM).

Several trials used an autologous tumor cells approach. One was a University of Leuven/Wurzburg Phase II trial [8] of a DC-based vaccine plus autologous tumor lysates to yield a median survival time from relapse of 0.8 years in recurrent GBM. Another Phase I trial [9] from Advanced Biotherapies used autologous tumor cells with a TGF-β2 antisense-modified tumor cell vaccine to yield a median survival time of 1.4 years (progressing GBM patients at enrollment). And still another Pahse II trail, this from Tvax Biomedical [10], used autologous whole tumor with GM-CSF growth support and adoptive transfer of CD3-activated lymphocytes, to yield median survival time = 1.0 years (recurrent malignant glioma).

In addition, Nigata university conducted a Phase I trial [11] of a personalized peptide vaccine, yielding median survival time = 1.7 years (recurrent GBM). And NABTC (North American Brain Tumor Coalition) sponsored a Phase II trial [12] of Poly-ICLC (polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose) yielding a median survival time og 1.4 years (newly diagnosed GBM).

LOOKING FORWARD

Note that these survival-endpoint trials are all either Phase I or Phase II, so I am eagerly awaiting the outcome of one of the first Phase III immunotherapy for GBM trials, the ACT IV Trial, an international, randomized double-blind controlled trial of Rindopepimut, a peptide vaccine (also known as PEPvIII-KLH/CDX-110) which elicits EGFRvIII-specific humoral and cellular immune responses, plus GM-CSF growth support along with adjuvant temozolomide (TMZ) in patients With newly diagnosed, surgically resected, EGFRvIII-positive GBM. This trial is particularly exciting since previous Phase I and Phase II clinical trials have demonstrated significantly higher progression-free (PFS) and overall survival (OS) times in vaccinated patients with EGFRvIII-expressing GBM tumors, especially in the ACT III [13] and the ACTIVATE Trial (discussed above), both yielding some of the best median OS results in GBM to date, of in excess of 2 years (24.6 in ACT III, and 26.o in the ACTIVATE Trial. Also I note that this trial is running in parallel with the Celldex Phase 2 ReACT Trial [14] of rindopepimut plus bevacizumab (Avastin) in recurrent glioblastoma. I am hoping that in the ACT IV Trial, the addition of TMZ may increase response rates in advanced disease, and push the outcomes even higher (possibly to near three years or better in immune responders, which would constitute a clinical therapeutic breakthrough in the immunotherapy of GBM.

Exciting times for the immunotherapeutic treatment of brain tumors!

REFERENCES

1. Sampson JH, Heimberger AB, Archer G, et al. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol. 2010;28:4722-4729.

2. Sampson JH, Archer GE, Bigner DD, et al. Effect of EGFRvIII-targeted vaccine (CDX-110) on immune response and TTP when given with simultaneous standard and continuous temozolomide in patients with GBM. J Clin Oncol (Meeting Abstracts) 2008;26:2011.

3. Sampson JH, Archer GE, Mitchell DA, et al. An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme. Mol Cancer Ther 2009;8:2773-2779.

4. Mitchell DA, Archer G, Bigner D, et al. RNA-loaded dendritic cells targeting cytomegalovirus in patients with malignant glioma. Neurooncology 2007;9:509.

5. Yu J, Liu G, Ying H, Yong W, Black K, Wheeler CJ. Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res 2004;64:4973-4979.

6. Wheeler CJ, Black KL, Liu G, et al. Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients. Cancer Res 2008;68:5955-5964.

7. Liau LM, Prins RM, Kiertscher SM, et al. Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res 2005;11:5515-5525.

8. De Vleeschouwer S, Fieuws S, Rutkowski S, et al. Postoperative adjuvant dendritic cell-based immunotherapy in patients with relapsed glioblastoma multiforme. Clin Cancer Res 2008;14:3098-3104.

9. Fakhrai H, Mantil JC, Liu L, et al. Phase I clinical trial of a TGF-b antisense-modified tumor cell vaccine in patients with advanced glioma. Cancer Gene Ther 2006;13:1052-1060.

10. Sloan AE, Dansey R, Zamorano L, et al. Adoptive immunotherapy in patients with recurrent malignant glioma: preliminary results of using autologous whole-tumor vaccine plus granulocyte-macrophage colony-stimulating factor and adoptive transfer of anti-CD3-activated lymphocytes. Neurosurg Focus 2000;9:e9.

11. Yajima N, Yamanaka R, Mine T, et al. Immunologic evaluation of personalized peptide vaccination for patients with advanced malignant glioma. Clin Cancer Res 2005;11:5900-5911.

12. Butowski N, Chang SM, Junck L, et al. A phase II clinical trial of poly-ICLC with radiation for adult patients with newly diagnosed supratentorial glioblastoma: a North American Brain Tumor Consortium (NABTC01–05). J Neurooncol 2009;91:175-182.

13. Lai RK, Recht LD, Reardon DA, et al. Long-term follow-up of ACT III: A Phase II trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma. Abstract IM-03. Neuro Oncol; SNO: 16th Annual Scientific Meeting of the Society for Neuro-Oncology in Conjunction with the AANS/CNS Section on Tumors; November 17–20, 2011; Orange County, CA. 2011. pp. iii34–iii40.

14. Reardon D, Vredenburgh J, Desjardins A, et al. REACT: A Phase II Study of Rindopepimut (CDX-110) plus Bevacizumab in Relapsed Glioblastoma. Presented at the 2012 ASCO annual Meeting.

There are vaccines for Gliboblastoma, however, they are still in clinical trails.

Many of these vaccines have shown great promise.

These vaccines function by activating the patient's immune system against the tumor.

http://cedars-sinai.edu/About-Us/News/News-Releases-2012/Study-Vaccine-targets-malignant-brain-cancer-antigens-significantly-lengthens-survival.aspx

Here is another example of an ongoing clinical trial:

http://www.activartis.com/en/research-and-development/gbm-vax-study.html

http://www.activartis.com/en/research-and-development/gbm-vax-study/gbm-vax-study-early-results.html