A patient-friendly review of Dendritic Cell Vaccines; these are usually made from a patient's own Dendritic Cells, which typically present a pathogen and even a cancer to the Adaptive Immune system to stimulate tailored T-cell production that can then attack the patient's cancer. This is a personalised treatment.
What is Dendritic Cell Therapy?
Dendritic Cell Vaccines, or Dendritic cell therapy, is another Alternative Cancer Therapy which is felt to be full of promise.
The body has two specific immune systems
* The Innate immune system - formed at birth, it sees most pathogens and can act against them, but is slow.
* The Adaptative Immune System - develops over time with each infection. It is the memory of your immune system.
Dendritic cells are unique cells in the Innate system that process then present pathogens or cancer cells to the T cells of the Adaptive System. They thus cause a specific, more tailored and more vigorous response in the T-cells to attack the original problem.
Dendritic cell vaccines are increasingly being used to treat cancers such as GBM in mainstream hospitals from The Preston Robert Tisch Cancer Center at Duke Medical School in Carolina to Cedars Sinai Medical Center in LA. The treatment, which is defined under the banner of 'immunotherapy' aims to increase the body's immune response against the cancer.
Dendritic cell vaccines (DCVs) are actually a slight misnomer. The idea of a vaccine to most people is something that prevents an illness in the first place. These vaccines are developed directly from the patient's own cancer cells (autologous vaccines), tailoring an immune response to try to attack that specific cancer. And Dr. Harmon Eyre, the VP of Research at the American Medical Association has stated his conviction: "Patients responses are far out of proportion to anything that any current therapy could do".
Probably the first use of Dendritic cell vaccines was at Stanford Cancer Institute where Dendritic cells (DCs) were isolated from patients with non-Hodgkins lymphoma. The DCs were loaded with immunoglobulins from the patients cancer cells. After re-injection a significant response was obtained from the T-cells and out of 6 patients, two had a complete response, with complete cancer regression.
Early Clinical Trials with non-Hodgkins lymphoma have taken place while other cancers have also been treated, for example multiple myeloma, prostate, colorectal and non-small cell lung cancer. Stanford say that "the treatment represents a promising and safe form of immunotherapy.
Go to: A patient-friendly review of the latest in immunotherapy treatments
Dendritic cells - what are they?
Dendritic cells are a part of the body's normal helper immune system, called the Antigen Presenting Cells, or APCs. They constantly sample the environment in the body looking for rogue cells and invaders, and then present a protein combination to the T- lymphocytes in the lymph nodes. This combination is thus specific to the rogue cell. Other helper cells cause the T-cells to become cytoxic (cell destroying), and an army of T-cells is then released from the lymph nodes looking for, and binding to the surface of, any cell that has the same specific protein combination.
So Dendritic cells are T-cells' messengers and primers. For example, after cell injury following an accident or damage to the tissues, a factor (the DNGR-1 receptor) on a Dendritic cell is activated and this mobilises the immune system to deal with the dead cells. In this event, Dendritic cells are the alarm; the early warning system.
In cancer, they don't seem to work very well because of a blocking protein first identified by the Fred Hutchinson Cancer Center and so their numbers are reduced.
But if the patients own Dendritic cells could be harvested from the patient's own blood or bone marrow, and then multiplied in the laboratory, a much more vibrant arrary of cells could better arm the T-cells. They are then injected back into the patient enhancing the T-cells briefing and encouraging a stronger , more specific attack.
A four country trial of a DC vaccine for GBM, was reported on in 2018. Taking more than 286 patients who had surgery, then temozolomide, the patients were either given an autologous tumour lysate-pulsed Dendritic Cell Vaccine DCVax-L or a placebo. Without the vaccine, the overall survival time was 23.3 months; with the vaccine, almost half the patient's survived 3 years, and those that survived had a predicted survival of 88.2 months.
Dendritic cell vaccines and immunotherapy
Some Dendritic vaccines are produced by fusing the patients cancer cells with Dendritic cells from other human donors. The Dendritic cells are loaded up with dying tumour cells, cancer cell RNA and other antigens before injecting them back into the patient. Dr Steinman of the Rockefeller Institute, in his address to the Baylor University Medical School sites two concerns that the loaded cells don't always provoke a T-cell response (something that Stanford in their work with non-Hodgkins have also found); and often they do not actually end up in the lymph nodes (the place where the T-cells multiply rapidly if stimulated). He sees more potential in trying to coax the Dendritic cells currently inside the body to take up cancer cells. This he does by making cancer cell vaccines and trying to upload them into the Dendritic cells; the Dendritic cells are known to have large numbers of receptor sites on their surface.
Joseph Baar of the Pittsburgh Cancer Institute reviewed Dendritic cell vaccine developments as long ago as 1999 in the Oncologist magazine. Clinical trials were originally developed for melanoma but have been extended to other cancers.
The work does have research behind it: Since the first clinical trial (Nestle FO, et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat. Med. 4 Mar 1998; 4(3):269-70) was published in 1998, the number of clinical trials with Dendritic cell vaccines for various types of cancer has been increasing rapidly worldwide. Provenge is a Dendritic Cell Vaccine from Dendreon with FDA approval for use with prostate cancer patients - we cover it in our drugs section. However it does had side effects and Clinical Trials show it extends life by a mean 4 months, but for some, considerably longer. Go to our A-Z guide to drugs to find out more.
There are also private options:
* The Issels Clinic currently uses a method of dendritic cell production and administration following the model pioneered by Richard L. Edelson and Carole L. Berger of Yale University. This painless procedure is also called transimmunization.
Most treatments are, however, private and thus the patient is reliant on the quality of the particular clinic. And the patients own financial status.
* The Dove Clinic in the UK offers this therapy.
Our bottom line
(Chris Woollams) If you read the former Royal Marsden's Professor Mike Brada and his interview on future treatments for brain tumours in icon and on this Website, he talks of the complex genetic understanding for Dendritic Cell Vaccines and how it is really improving. He says that the brain does not have many dendritic cells and so new, extremely clever and complex ways of working are being developed. But in fact, the Preston Robert Tisch Center at Duke Medical Center in Carolina used it experimentally with brain cancer patients more than 10 years ago for brain tumour patients. (See Amy's Story - CLICK HERE)
For quite a while Dendritic Cell Therapy has been full of promise but short on delivery. One figure we saw was that it worked in only 12% of patients. Clearly that is all changing with more autologos use, more understanding and more Clinical Trials.
Overall, there's little doubt Immunotherapy is flavour of the year. We will see just how well it develops".
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