First, how things are happening inside our body is so complex, and so is how our immune system works. It is beyond my comprehension. Notwithstanding that I do not understand how the immune system works, this is what I have learned from the internet about dendritic cells and dendritic therapy.
The dendritic cell was termed by Dr. Ralph Steinman of Rockefeller University, who was awarded a Nobel prize in 2011 for the discovery of dendritic cell as a key antigen-presenting cell (APC) to help activate T-cells in our immune system.
Our immune system consists of innate (natural, nonspecific) immunity and adopted (acquired, specific) immunity. All immune cells are produced in the bone marrow. So, we are born with innate immunity, which includes many different immune cells, which include neutrophils, natural killer cells, macrophages, dendritic cells, and etc. innate immune cells attack blindly whatever foreign pathogens come into our body. Most innate immune cells are constantly flowing in our blood as a part of white blood cells (WBC) and as soon as
some pathogen invades our body, they try to prevent an expansion of pathogens and try to kill them. Dendritic cells, after they mature in the bone marrow, move to different parts of our body through blood vessels and stay put mainly in soft tissue, e.g. connective tissue just below urothelial tissue in the bladder, until the invasion of the pathogens nearby. Dendritic cells are like a border patrol on a motorcycle. Their main role is to find the invaders, get the information about the invaders, and drive through lymphatic vessels to the nearby control centers ( lymph nodes) where adopted immune cells are stationed. There, dendritic cells give the information about the invaders to the chief of the control center, which is T-helper cells (CD-4+), then T-helper dispatches anti-bodies from B-cells and T-killer cells (CD-8+) with a specific profile of the invaders. Antibodies and T-cells travel through blood vessels. It will take 5-7 days before T-killer cells arrive at the location of the invasion. T-killer cells are the main immune cells that will kill the invaded cells, which can be cancer cells if the profile which T-cells had received from dendritic cells is cancer. The pofile is called antigens.
Dr. Steinman thought if he could get the profile of the target cancer cells and gave it dendritic cells, then the dendritic cells would pass the profile to T-cells and would activate T-cells to kill the cancer cells which had the specific profile that the dendritic cells had informed. Dr. Steinman thought he could make the vaccine for cancer that way. He dedicated his research to dendritic-based cancer and AIDS vaccine for over 30 years. He saw some success in treating cancers in mice. In 2007, Dr. Steinman was diagnosed with pancreatic cancer. Then, he and his colleagues received special permission to test the dendritic therapy to treat his cancer in addition to his getting Gemcitabine chemotherapy. Sadly, he died 3 days before the Nobel prize committee announced his receiving a Nobel prize in 2011.
So far, the only FDA-approved dendritic therapy for cancer is PROVENGE. PROVENGE which was developed by the company Dendreon. Dendreon was founded by Edgar Engleman and Samuel Strober based on the research performed in their laboratories at the Stanford University School of Medicine. PROVENGE was approved by FDA in 2010 for the treatment of advanced prostate cancer. PROVENGE uses PSA as antigen, which is found in 95% of prostate cancer patients. The process of producing PROVENGE is to get dendritic cells from the patient, multiply dendritic cells and attach the PSA antigen to the dendritic cells in the lab, and inject it back to the patient. At present, the whole process takes three days and requires three treatments. The cost for the treatment is about US$100,000. PROVENGE is recommended only for an early stage of advanced prostate cancer of which the PSA is less than or equal to 22.1 ng/mL. So, the efficacy of PROVENGE was not as high as initially hoped for.
The challenge of dendritic cell therapy is that the dendritic cells must be obtained from the patient, otherwise, our immune system kills the dendritic cells as a foreign pathogen. Also, the FDA's requirement for quality control in each step of the manufacturing process is strict. Too expensive to develop dendritic cell therapy. So, Dr. Edgar Engleman was proposing to make dendritic cells with specific antigens in-situ, which means produce the dendritic cells with antigens inside the body without taking them out from the body, multiplying in the lab, and put them back to the body. That was 2016. I do not know how is progressing.
In terms of the side effects of PROVENGE in addition to other PROVENGE-related information, it can be obtained in the FDA site.
"Common adverse reactions reported during a safety evaluation of 601 patients who received PROVENGE were chills, fatigue, fever, back pain, nausea, joint ache, and headache. The majority of adverse reactions were mild or moderate in severity. Serious adverse reactions that were reported in patients receiving PROVENGE included some acute infusion reactions and stroke."
www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/questions-and-answers-provenge
There are several studies and development of the dendritic cell therapy for Melanoma, Colon Cancer but I was not able to locate any study for bladder cancer.
Also, interestingly, I have noticed that there are a few private institutes in Germany, Denmark, and India that are providing dendritic cell therapy.
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