Anti-CMV Dendritic Cell Vaccine

Property	Information
Drug Name	Anti-CMV Dendritic Cell Vaccine
FDA Approval	In clinical trials; not yet FDA-approved
Used for	Newly diagnosed and recurrent Glioblastoma Multiforme (GBM)
Clinical Trial Phase	Phase II
Clinical Trial Explanation	Not specified
Common Side Effects	Not detailed; dendritic cell vaccines are generally well-tolerated with mild side effects.
OS without	Historical controls indicate median overall survival around 15-17 months for newly diagnosed GBM.
OS with	Varied; one study showed median OS of 41.1 months with vaccine and temozolomide, and another indicated 30.3 months with vaccine and basiliximod.
PFS without	Typically around 6-7 months for standard GBM treatments.
PFS with	Impressive 25.3 months in a study combining vaccine with dose-intense temozolomide.
Usefulness Rating	4
Usefulness Explanation	This vaccine represents a promising strategy by targeting CMV antigens present in GBM cells, potentially extending survival significantly beyond standard treatments. Initial results suggest substantial benefits for certain patient groups.
Toxicity Level	2
Toxicity Explanation	Dendritic cell vaccines like this one are known for their favorable safety profile, with predominantly mild, manageable adverse effects.

From Ben Williams Book: This approach relies on the finding that most GBM tumors are infected with the cytomegalovirus, a common herpes virus. GBMs have a high incidence of the virus being present (by some estimates over 90%) whereas normal brain cells do not. The new treatment approach involves targeting a specific protein component of the CMV virus, which then kills the virus and the cell harboring it.

Results of a small trial for Duke’s anti-CMV dendritic cell vaccine with or without preconditioning with an injection of tetanus/diptheria toxoid was published in Nature in March 2015 (320). There were 6 newly diagnosed glioblastoma patients in each arm. In the 6 patients treated with the vaccine but without tetanus/diptheria preconditioning, median progression-free and overall survival freom diagnosis was 10.8 and 18.5, not significantly better than historical controls. In the group of patients receiving preconditioning of the injection site with tetanus/diptheria, three of the patients were alive without disease progression at 44-47 months from diagnosis. A Wall Street Journal article published at the same time as the Nature study gave more up-to-date information, revealing that two of these longer-term survivors had died at nearly 5 and 6 years from diagnosis, while the remaining patient was still alive over 8 years from diagnosis. An update from the 2016 AANS conference revealed that this patient was still alive without tumor regrowth at 120 months (10 years). The purpose of the tetanus/diptheria booster is to improve migration of the dendritic cells to lymph nodes. Despite the striking success of the anti-CMV dendritic cell vaccine combined with a tetanus/diptheria booster injection, a randomized phase 2 trial is scheduled to open in 2015 with one arm randomized to receive the tetanus/diptheria toxoid preconditioning, and the other arm randomized to

receive saline (essentially placebo). Both arms receive the anti-CMV dendritic cell vaccine (trial NCT02366728).

A second single-arm phase II trial (ATTAC-GM) combined dose-intense temozolomide (100 mg/mz2 for 21 days of a 28 day cycle) with anti-CMV dendritic cell vaccine and tetanus preconditioning. Median progression-free and overall survival for the 11 patients was a remarkable 25.3 and 41.1 months. This data was presented at the 2016 annual AANS meeting by Kristen Batich.

A separate trial (NCT00626483) at Duke for newly diagnosed glioblastoma is testing the CMV-targeted dendritic cell vaccine in combination with basiliximab, a CD25 antibody intended to inhibit the regulatory T-cell (Treg) population. In an abstract published for the ASCO 2015 meeting, we can read that in a pilot study of seven patients treated with this combination therapy, median progression-free and overall survival was an impressive 23.5 and 30.3 months respectively.

Currently recruiting clinical trials testing CMV pp65 vaccines with or without tetanus/diptheria preconditioning or basiliximab include the ELEVATE trial at Duke University (NCT02366728), the PERFORMANCE trial also at Duke (NCT02864368), the ATTAC-II trial at the University of Florida (NCT02465268), and the AVERT trial for recurrent grade III glioma and GBM at Duke University (NCT02529072).Property "Has original text" (as page type) with input value "This approach relies on the finding that most GBM tumors are infected with the</br>cytomegalovirus, a common herpes virus. GBMs have a high incidence of the virus being</br>present (by some estimates over 90%) whereas normal brain cells do not. The new</br>treatment approach involves targeting a specific protein component of the CMV virus,</br>which then kills the virus and the cell harboring it.</br></br>Results of a small trial for Duke’s anti-CMV dendritic cell vaccine with or without</br>preconditioning with an injection of tetanus/diptheria toxoid was published in Nature in</br>March 2015 (320). There were 6 newly diagnosed glioblastoma patients in each arm. In</br>the 6 patients treated with the vaccine but without tetanus/diptheria preconditioning,</br>median progression-free and overall survival freom diagnosis was 10.8 and 18.5, not</br>significantly better than historical controls. In the group of patients receiving</br>preconditioning of the injection site with tetanus/diptheria, three of the patients were</br>alive without disease progression at 44-47 months from diagnosis. A Wall Street Journal</br>article published at the same time as the Nature study gave more up-to-date information,</br>revealing that two of these longer-term survivors had died at nearly 5 and 6 years from</br>diagnosis, while the remaining patient was still alive over 8 years from diagnosis. An</br>update from the 2016 AANS conference revealed that this patient was still alive without</br>tumor regrowth at 120 months (10 years). The purpose of the tetanus/diptheria booster is</br>to improve migration of the dendritic cells to lymph nodes. Despite the striking success of</br>the anti-CMV dendritic cell vaccine combined with a tetanus/diptheria booster injection,</br>a randomized phase 2 trial is scheduled to open in 2015 with one arm randomized to</br>receive the tetanus/diptheria toxoid preconditioning, and the other arm randomized to</br></br>receive saline (essentially placebo). Both arms receive the anti-CMV dendritic cell vaccine</br>(trial NCT02366728).</br></br>A second single-arm phase II trial (ATTAC-GM) combined dose-intense temozolomide</br>(100 mg/mz2 for 21 days of a 28 day cycle) with anti-CMV dendritic cell vaccine and</br>tetanus preconditioning. Median progression-free and overall survival for the 11 patients</br>was a remarkable 25.3 and 41.1 months. This data was presented at the 2016 annual</br>AANS meeting by Kristen Batich.</br></br>A separate trial (NCT00626483) at Duke for newly diagnosed glioblastoma is testing the</br>CMV-targeted dendritic cell vaccine in combination with basiliximab, a CD25 antibody</br>intended to inhibit the regulatory T-cell (Treg) population. In an abstract published for</br>the ASCO 2015 meeting, we can read that in a pilot study of seven patients treated with</br>this combination therapy, median progression-free and overall survival was an impressive</br>23.5 and 30.3 months respectively.</br></br>Currently recruiting clinical trials testing CMV pp65 vaccines with or without</br>tetanus/diptheria preconditioning or basiliximab include the ELEVATE trial at Duke</br>University (NCT02366728), the PERFORMANCE trial also at Duke (NCT02864368), the</br>ATTAC-II trial at the University of Florida (NCT02465268), and the AVERT trial for</br>recurrent grade III glioma and GBM at Duke University (NCT02529072)." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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