Dendritic Cell Vaccine (DCVax-L)
Links: https://www.onclive.com/view/dcvax-l-improves-survival-in-glioblastoma, https://medicalxpress.com/news/2022-11-phase-clinical-trial-brain-cancer.html, https://www.targetedonc.com/view/dcvax-l-extends-survival-in-newly-diagnosed-and-recurrent-gbm
From Ben Williams Book: Methods to enhance the detection of tumor antigens are now the subject of intensive research, for various types of cancer. The most successful approach to date involves the use of dendritic cells, which have been characterized as "professional antigen-presenting cells". Dendritic cells are extracted from the blood, then co-cultured with a lysate prepared from cells from the patient's tumor, and stimulated with granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (GM-CSF is the growth factor used to counteract the decrease in white-cell blood counts due to chemotherapy). This growth factor causes the mixture of tumor and dendritic cells to be expanded as well. This mixture is then injected into the patient, evoking an increased reaction from the immune system.
This use of dendritic cells has been applied to several different types of cancers. Its use with brain cancer was pioneered by Dr. Keith Black and his team at UCLA, then continued at Cedars Sinai when Dr. Black’s team moved to that institution. A separate program at UCLA was continued by Dr. Linda Liau. Other centers using this approach are in Belgium, China, and Japan. In one of the first small clinical trials (149) nine newly �diagnosed high-grade glioma patients received three separate vaccinations spaced two weeks apart. Robust infiltration of T cells was detected in tumor specimens, and median survival was 455 days (compared to 257 days for a control population). A subsequent report (150) involving 8 GBM patients produced a median survival time of 133 weeks, compared to a median survival of 30 weeks of a comparable set of patients receiving other treatment protocols. At two years 44% of patients were progression free, compared to only 11% of patients treated with the gold standard of Temodar during radiation and thereafter. An excellent review of the clinical outcomes and technical issues associated with the vaccine trials is provided by Wheeler and Black (151).
In the largest of the initial clinical trials (152), 34 GBM patients (23 with recurrent tumors, 11 newly diagnosed) were assessed for their immunological response to the vaccine using interferon production as the measure, with the result that only 50% of patients exhibited a response. The degree of response was moderately correlated with survival time: 642 days for responders, 430 days for nonresponders. Five of the 34 patients were alive at the time of the report, with survival times ranging from 910 to 1216 days, all of whom were classified as immunological responders. It should be noted that the average age of patients in this trial was 52 years, only slightly lower than the typical GBM population, whereas many of the other vaccine trials have included mainly younger patients.
Among the most promising results using lysate-pulsed dendritic cell vaccines has come from the UCLA research program led by Dr. Liau. In the most detailed report of the results (153) 15 newly diagnosed GBM patients and 8 patients with recurrent tumors (average age =51), received the initial dendritic vaccine (followed by three booster vaccines in combination with either POLY ICLC or imiquimod (applied locally to the injection site). For all patients, median time to progression was 15.9 months. Median survival time for newly diagnosed patients was 35.9 months, and 2- and 3-year survival rates were 77% and 58%. For recurrent patients, mean survival from the time of initial enrollment in the trial was 17.9 months. Subsequent reports have come from press releases from Northwest Biotherapeutics, the biotech company sponsoring the DCVax trials. Survival at four years has been 33 %, and 27% have exceeded six years (154). Currently underway is a large multi-center phase III trial.
As of July 2015, no outcomes from the phase 3 DCVax-L trial have yet been made public, though patient outcomes from an “informational arm” receiving DCVax-L were published by Northwest Biotherapeutics in March (see press release here). This informational arm consisted of 51 patients who had enrolled into the phase 3 trial, but were excluded from the trial due to early disease progression prior to the first vaccination. The patients received the DCVax injections and were followed up on a Compassionate Use basis. Survival outcomes in this group are summarized on a youtube video featuring Marnix Bosch, the company’s Chief Technical Officer. Within this group of 51 patients was a �subgroup of 25 patients considered to be “indeterminate”, meaning that they had evidence of disease progression at the baseline visit (rendering them ineligible for the trial), but subsequently had either stable disease, modest progression, or modest regression. This group of patients is reported to have a median survival of 21.5 months (the report does not make clear whether this is from surgery or from randomization post-radiation). As of March 2015, nine of these patients were still alive after 24 months of follow-up, six of these nine were alive after 30 months of follow-up, and four of these nine are alive at 35 to over 40 months. Therefore we can expect that median survival in the phase 3 trial (patients without disease progression at the baseline visit) will be at least greater than 21.5 months.Property "Has original text" (as page type) with input value "Methods to enhance the detection of tumor antigens are now the subject of intensive</br>research, for various types of cancer. The most successful approach to date involves the</br>use of dendritic cells, which have been characterized as "professional antigen-presenting</br>cells". Dendritic cells are extracted from the blood, then co-cultured with a lysate</br>prepared from cells from the patient's tumor, and stimulated with granulocyte</br>macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (GM-CSF is the</br>growth factor used to counteract the decrease in white-cell blood counts due to</br>chemotherapy). This growth factor causes the mixture of tumor and dendritic cells to be</br>expanded as well. This mixture is then injected into the patient, evoking an increased</br>reaction from the immune system.</br></br>This use of dendritic cells has been applied to several different types of cancers. Its use</br>with brain cancer was pioneered by Dr. Keith Black and his team at UCLA, then</br>continued at Cedars Sinai when Dr. Black’s team moved to that institution. A separate</br>program at UCLA was continued by Dr. Linda Liau. Other centers using this approach</br>are in Belgium, China, and Japan. In one of the first small clinical trials (149) nine newly</br>�diagnosed high-grade glioma patients received three separate vaccinations spaced two</br>weeks apart. Robust infiltration of T cells was detected in tumor specimens, and median</br>survival was 455 days (compared to 257 days for a control population). A subsequent</br>report (150) involving 8 GBM patients produced a median survival time of 133 weeks,</br>compared to a median survival of 30 weeks of a comparable set of patients receiving</br>other treatment protocols. At two years 44% of patients were progression free, compared</br>to only 11% of patients treated with the gold standard of Temodar during radiation and</br>thereafter. An excellent review of the clinical outcomes and technical issues associated</br>with the vaccine trials is provided by Wheeler and Black (151).</br></br>In the largest of the initial clinical trials (152), 34 GBM patients (23 with recurrent</br>tumors, 11 newly diagnosed) were assessed for their immunological response to the</br>vaccine using interferon production as the measure, with the result that only 50% of</br>patients exhibited a response. The degree of response was moderately correlated with</br>survival time: 642 days for responders, 430 days for nonresponders. Five of the 34</br>patients were alive at the time of the report, with survival times ranging from 910 to 1216</br>days, all of whom were classified as immunological responders. It should be noted that</br>the average age of patients in this trial was 52 years, only slightly lower than the typical</br>GBM population, whereas many of the other vaccine trials have included mainly younger</br>patients.</br></br>Among the most promising results using lysate-pulsed dendritic cell vaccines has come</br>from the UCLA research program led by Dr. Liau. In the most detailed report of the</br>results (153) 15 newly diagnosed GBM patients and 8 patients with recurrent tumors</br>(average age =51), received the initial dendritic vaccine (followed by three booster</br>vaccines in combination with either POLY ICLC or imiquimod (applied locally to the</br>injection site). For all patients, median time to progression was 15.9 months. Median</br>survival time for newly diagnosed patients was 35.9 months, and 2- and 3-year survival</br>rates were 77% and 58%. For recurrent patients, mean survival from the time of initial</br>enrollment in the trial was 17.9 months. Subsequent reports have come from press</br>releases from Northwest Biotherapeutics, the biotech company sponsoring the DCVax</br>trials. Survival at four years has been 33 %, and 27% have exceeded six years (154).</br>Currently underway is a large multi-center phase III trial.</br></br>As of July 2015, no outcomes from the phase 3 DCVax-L trial have yet been made public,</br>though patient outcomes from an “informational arm” receiving DCVax-L were published</br>by Northwest Biotherapeutics in March (see press release here). This informational arm</br>consisted of 51 patients who had enrolled into the phase 3 trial, but were excluded from</br>the trial due to early disease progression prior to the first vaccination. The patients</br>received the DCVax injections and were followed up on a Compassionate Use basis.</br>Survival outcomes in this group are summarized on a youtube video featuring Marnix</br>Bosch, the company’s Chief Technical Officer. Within this group of 51 patients was a</br>�subgroup of 25 patients considered to be “indeterminate”, meaning that they had</br>evidence of disease progression at the baseline visit (rendering them ineligible for the</br>trial), but subsequently had either stable disease, modest progression, or modest</br>regression. This group of patients is reported to have a median survival of 21.5 months</br>(the report does not make clear whether this is from surgery or from randomization</br>post-radiation). As of March 2015, nine of these patients were still alive after 24 months</br>of follow-up, six of these nine were alive after 30 months of follow-up, and four of these</br>nine are alive at 35 to over 40 months. Therefore we can expect that median survival in</br>the phase 3 trial (patients without disease progression at the baseline visit) will be at least</br>greater than 21.5 months." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
