A review on Dendritic Cell Vaccines and Dendritic Cell Therapy
What is it?
Dendritic Cell Vaccines, or Dendritic cell therapy, is another ´Alternative´ Cancer Therapy which is felt to be full of promise. Dendritic cells are unique antigen-producing cells, capable of sensitising T-cells to both new and existing antigens. In English that means they help prepare the T-cells so that they can attack the bad guys. (Chris Woollams)
Dendritic cell vaccines are increasingly being used to treat cancer 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 ever occurring. These vaccines are developed directly from the patients illness, tailoring an immune response to try to kick out that particular 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-Hodgkin´s 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-Hodgkin´s 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´.
For a review of Immunotherapy, CLICK HERE
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´ little helpers. 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. Dendritic cells are the alarm; the early warning system.
In cancer, they don´t seem to work very well because of the protein identified by the Fred Hutchinson Cancer centre and so their numbers are reduced.
But if the patient´s own Dendritic cells could be harvested from the patient´s own blood or bone marrow, and then multiplied in the laboratory, the theory runs that they would have some recognition of the cancer. To inject vast numbers of them back into the body with the cancer should see the cancer take a serious hit.
Dendritic cell vaccines and immunotherapy
Most Dendritic vaccines are produced by fusing the patient´s 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-Hodgkin´s 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.
In the UK, The Dove Clinic 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)
This leads to my concern. Dendritic cell therapy has experts who are fans and, of that there´s no doubt. But, it seems inexplicably, it simply does not work with quite a large number of people. False hope is thus something to avoid, especially if coupled with the expense of private treatment. It all seems very clever, but early days and a bit ´hit or miss´. Indeed, I have read reports that say that you can prepare the correct rogue cell/dendritic cell combination and put it back in the patient but get poor uptake from the T-cells in the lymph nodes. Perhaps I am wrong; perhaps the launch of Provenge proves me wrong. But, as yet there don´t seem to be the strong and robust Clinical Trials orthodox medicine normally demands, yet treatment in Hospitals and cancer clinics goes ahead.
Overall, there´s no doubt Immunotherapy is flavour of the year. We will see how it develops.
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