Autologous T cell Therapy for Cytomegalovirus as a Consolidative Treatment for Recurrent Glioblastoma

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Charles S. Cobbs MD

The Gregory Foltz, MD Endowed Director Ben & Catherine Ivy Center for Advanced Brain Tumor Treatment Swedish Neuroscience Specialists

 

Recently, a colleague of mine, Dr. Rajiv Khanna in Brisbane, Australia published an exciting paper in the journal Cancer Researchhttp://cancerres.aacrjournals.org/content/early/2014/05/07/0008-5472.CAN-14-0296.abstract .  Dr. Khanna and his group have extensive experience in the esoteric area of virus associated malignancy. He has worked for 25 years in this area, and has worked with Epstein-Barr Virus (EBV) related malignancies that have responded to vaccine treatments.  Because of his expertise in this area, he became interested in the concept that human cytomegalovirus (CMV), which our group demonstrated to be associated with glioblastoma, might be a good target for reactivation of an immune response that could lead to killing of glioblastoma cells. Dr. Khanna and his group identified patients with recurrent glioblastoma who had antibody responses to CMV, indicating a prior exposure. From this group of 19 patients they were able to remove the T cells (which are the important immune cells that are known to fight both cancer and viral infection), and study their  T cells to determine if they had a functional immune  response against CMV.   In almost any person that has been exposed to CMV in the past, which is about 80% of adults and most countries, prior exposure to CMV induces a robust T-cell response.  So, if you take T cells from a patient who has been exposed to CMV and expose those cells in a dish to CMV proteins, the T cells normally will produce multiple cytokines (chemicals that ramp up the immune response), which are critical for a complete immune response.  Dr. Khanna found that in patients with glioblastoma, their T cells exhibited deficiencies in their ability to be activated and to produce all of the important cytokines required for a normal immune response to CMV infection. Furthermore, in these patients with recurrent glioblastoma who were normally expected to live only a few months, Dr. Khanna and his team were able to restore a potent immune response to CMV by taking the patient’s own T cells and mixing them in a dish with other immune cells that were already stimulated to fight CMV.  These newly “fired  up” anti-CMV T cells were then frozen down and then given back to the patient as a vaccine.  Interestingly, in this relatively small phase I study with only a dozen or so patients, there was a striking improvement in survival.  It should be noted that this study was not statistically weighted in order to provide  meaningful survival data. Nevertheless , the data at this point is intriguing.  The overall survival for these patients ranged from 133 to 2,428 days.  The median survival of all of these patients was 403 days, over a year.  Most interestingly, four of the 10 patients that completed the treatment remained progression free for the entire study (over several years).  The authors concluded that their  study shows that combination therapy with autologous CMV specific T cells and chemotherapy is a safe novel treatment option and may offer clinical benefit for recurrent glioblastoma patients.                         Disclaimer: This is a personal blog. Any views or opinions represented in this blog are personal and belong solely to the blog author and do not represent those of people, institutions or organizations that the owner may or may not be associated with in professional or personal capacity, unless explicitly stated.  All content provided on this blog is for informational purposes only. The owner of this blog makes no representations as to the accuracy or completeness of any information on this site or found by following any link on this site. The owner will not be liable for any errors or omissions in this information nor for the availability of this information. The owner will not be liable for any losses, injuries, or damages from the display or use of this information. These terms and conditions of use are subject to change at anytime and without notice. All content provided on this blog is for informational purposes only. The owner of this blog makes no representations as to the accuracy or completeness of any information on this site or found by following any link on this site. The owner will not be liable for any errors or omissions in this information nor for the availability of this information. The owner will not be liable for any losses, injuries, or damages from the display or use of this information.

One comment:

  1. Dear Dr. Cobbs,

    My son was diagnosed 10 months ago with Diffused Pontine Intrinsic Glioma. We have used all available means (standard radiation, temodal, cyberknife, Avastin) but it seems that nothing worked… Do you think that using Valcyte may add something? Please, do not remind me the prognosis for this disease… I know it from day 1 but I still believe that we will find the miracle that we are looking for…

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