The DCVax technology includes several product lines: DCVax-L for patients with solid tumors that are resectable (can be surgically removed), DCVax-Direct for patients with unresectable tumors, and DCVax-Prostate designed specifically for prostate cancer patients.
The technology (DCVax-L) is in one ongoing and advanced clinical trial; two other planned studies have not begun enrolling patients and their status is unclear.
How DCVax works
DCVax uses a patient’s own immune cells to fight cancer. In contrast to other immunotherapies that train T-cells to attack a single target on cancer cells, DCVax uses different types of immune cells to recognize different targets. In addition, DCVax engages more than just immune cells; it also mobilizes signaling molecules (such as cytokines) with the aim of involving the entire immune system.
All DCVax products use the patient’s immune cells to create a vaccine that boosts the immune system’s response to cancer cells, but there are differences in the way they are made and how they are given to the patient.
DCVax-L, for use in patients with solid and removable tumors, is made by collecting immune cells called monocytes from a patient’s blood. Thes monocytes are then grown in the laboratory to mature into dendritic cells, master immune cells that activate and coordinate immune responses.
As the dendritic cells mature they are “educated” to recognize biomarkers, or proteins specifically associated with the patient’s tumor, which are harvested from cancer cells collected from the patient’s tumor during surgery.
The mature, “educated” dendritic cells are then injected back into the patient. Once in the bloodstream, the “educated” dendritic cells recruit other immune cells and “teach” them to attack cancer cells. Because the activated, these “educated” immune cells multiply by themselves inside the body, with the intent of allowing small doses to yield a large and long-lasting response.
DCVax-L in clinical trials
DCVax-L is currently being tested in in patients with metastatic ovarian cancer and glioblastoma multiforme (GBM, one of the deadliest forms of brain cancer).
A Phase 3 trial (NCT00045968) to evaluate the effect of DCVax-L on disease progression and survival in adult patients with newly diagnosed GBM began in 2006 and is close to completion. For the trial, 331 participants have been randomized to receive up to 10 treatments, two injections per treatment, of either DCVax-L or placebo for up to 10 years. The multicenter trial has over 50 sites across the U.S., the UK, and Germany, but is no longer recruiting participants.
On Feb. 6, 2017, Northwest Biotherapeutics announced that the U.S. Food and Drug Administration (FDA) had lifted a partial clinical hold placed on the Phase 3 trial. A partial clinical hold is a delay or suspension of some aspects of a trial to provide time to the FDA to gather or review additional information or data. The lifting allowed the trial to continue, although a final 17 patients were not enrolled and the study is continuing with 331 participants. The company announced in September that independent analysis of trial data showed “encouraging projections” of median overall survival and progression free survival.
A previous Phase 1/2 trial of DCVax-L in patients with new or returned GBM reported that DCVax-L, when given alongside standard of care treatment, increased progression-free survival and overall survival beyond what is expected with standard of care alone.
A Phase 1 trial (NCT00683241) tested the safety and feasibility of using DCVax-L, combined with Avastin (bevacizumab) and cyclophosphamide, to treat about 36 women with recurrent epithelial ovarian cancer or primary peritoneal cancer. The trial assessed how the immune system responded to the vaccine.
DCVax-Direct also collects monocytes from the patient’s blood, but these are not fully matured into dendritic cells in the laboratory. Instead, they are injected directly into the tumor inside the body, and are designed to encounter the cancer biomarkers and mature into “educated” dendritic cells that “educate” and activate the rest of the immune system to fight cancer cells.
DCVax-Direct in clinical trials
A Phase 1/2 clinical trial (NCT01882946) was initiated, and aimed to enroll about 60 patients with unresectable solid tumors, including liver, colorectal, pancreatic, and skin (melanoma) cancers. Its stated purpose is to evaluate the safety of DCVax-Direct, how the tumor responds to treatment, and how long patients survive with and without tumor progression. The status of this trial, however, is not clear or known.
DCVax-Prostate is designed to treat patients with late-stage prostate cancer that is not treatable with hormones. Because this type of cancer has spread beyond the prostate, there is no distinct tumor, cancer cells that can be harvested to make DCVax and DCVax cannot be injected directly into the tumor. To make DCVax-Prostate, prostate-specific membrane antigen (PSMA), a protein found in almost all advanced prostate cancers, is produced in the laboratory and used to “educate” the patient’s dendritic cells.
DCVax-Prostate in clinical trials
A randomized Phase 3 clinical trial (NCT00043212) is intended to test the safety and effectiveness of DCVax-Prostate in men with hormone-refractory prostate cancer (cancer that does not respond to hormone treatment). The trial was cleared by the FDA, but withdrawn prior to enrollment and is not active. Northwest Biotherapeutics states on its website that it is looking to partner with another company to proceed with this trial.
The company reports that, to date,no patient treated with DCVax has experienced any serious adverse events.
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