"The potential to harness the effectiveness and specificity of the immune system underlies the growing interest in cancer immunotherapy. One such approach uses bone marrow-derived dendritic cells (DCs), phenotypically distinct and very potent antigen-presenting cells, to present tumour-associated antigens (TAAgs) and, thereby, generate tumour-specific immunity.
Many observations have led to clinical trials designed to investigate the immunological and clinical effects of Ag-pulsed DCs administered as a therapeutic vaccine to patients with cancer.
Although current DC-based vaccination methods are cumbersome and complex, promising preliminary results from clinical trials in patients with malignant lymphoma, melanoma, and prostate cancer suggest that immuno-therapeutic strategies, that take advantage of the unique properties of DCs, may ultimately prove both efficacious and widely applicable treatment in patients with cancer. "
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Dendritic Cell Therapy is something to learn all you can about.. remember to gather all the information you can from many different sources and use your intuition, Make your own decision based on what you, yourself have gathered and learned.
R
The interaction between tumour cells and the host immune system are complex, involving a multitude of cell types and mediators. Immune system has the potential to eliminate neoplastic cells, as evidenced by rare but well documented instances of spontaneous remissions (with no or inadequate treatment) in renal cell carcinoma and melanoma. Also, chronically and severely immunosuppressed individuals (transplantation recipients, congenital immune deficiency states and AIDS patients) exhibit an increased incidence of putative virallyinduced neoplasms; presence of AIDS-associated tumours correlate with the degree of immunosuppression.
Induction of effective tumour immunity can be viewed as a three-step process that includes：
appropriate presentation of tumour-associated antigens (TAAgs),
selection and activation of TAAg-specific T cells as well as non-Ag-specific effectors and
homing of TAAg-specific T cells to the tumour site and effective elimination of malignant cells expressing the TAAgs. Cancers may escape immune surveillance due to changes in and modulation of these various processes.
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The establishment of an effective anti-tumour response is a complex process. Initially, peptides associated with malignant cells must be located and recognised by T cells circulating in the blood stream and permeating tissues. Most solid cancers express small amounts of TAAgs, which may also be cryptic and not readily available for recognition by rare T cell clones, through a low affinity T cell receptor (TCR) complex. Moreover, tumour cells tend to lack co-stimulatory molecules that drive clonal expansion of T cells, the production of key regulatory cytokines, and development into tumour cell specific cytotoxic T lymphocytes (CTLs).
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Eliciting an effective anti-cancer response and removal of malignant cells is a complex biological process.
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Escape from immune surveillance is believed to be a fundamental biological feature of malignant disease in man, which contributes to uncontrolled tumour growth, eventually leading to death of the host. Defects in immune response in patients with a variety of tumours have been well documented. These defects have been ascribed mostly to suppressor cell function. Some authors have shown defective function of macrophages in malignant disease. In recent studies, it has been shown that a distinct subset of IA+ epidermal APCs appear capable of inducing tolerance to tumour Ags and that activated macrophages may induce structural abnormalities of the TCR-CD3 complex.
Future clinical trials with dendritic cells pulsed with tumor epitopes derived from newly identified tumor-associated peptides, RNA, lystates, and apoptotic bodies. Dendritic cells might also be genetically modified with cDNA encoding.
Some studies in humans with solid cancers have investigated DC trafficking in peripheral blood. It was showed that DCs in the peripheral blood of patients with head and neck cancer were significantly immunosuppressed. There was also an increased intratumoural presence of the immunosuppressive CD34+ progenitor cells. Patients with head and neck squamous cell carcinoma also had increased levels of the immunosuppressive peripheral blood CD34+ cells.
Defects in response to tetanus toxoid and influenza virus were observed in patients with advanced breast cancer. Dendritic cells isolated from patients with breast cancer demonstrated a significantly decreased ability to stimulate control allogeneic T cells. Data suggest that reduced DC function could be a major cause for the observed defect in cellular immunity documented in the patients with breast cancer.
Patients whose melanoma were responding (rM) to chemotherapy had DCs which were five times more potent inducers of allogeneic T cell proliferation than those patients whose tumours were progressing (pM). Phenotypic analysis showed a marked depression of CD86 expression on DCs in the latter patients. Culture supernatants from pM showed production of a TH2-type cytokine profile (IL-10), whereas a TH1-type cytokine profile (IL-2, IL-12 and interferon-gamma (IFN-gamma) was found predominantly in patients whose melanomas had responded to treatment.There is evidence that shows that dendritic cell function was inhibited by soluble factors present in melanoma cell cultures.
DCs from patients with hepatocellular carcinoma had significantly lower capacity to stimulate allogeneic T cell proliferation, compared with DCs isolated from patients with liver cirrhosis and normal controls. In patients with hepatocellular carcinoma, DCs expressed significantly lower levels of HLA-DR and induction of IL-12 production. On the other hand, DCs from such donors produced significantly higher levels of nitric oxide and tumour necrosis factor-alpha (TNF-alpha) compared with DCs from donors with liver cirrhosis and normal controls. These results confirm a defect of DC maturation in patients with established hepatocellular carcinoma and probably during carcinogenesis and tumour induction.
Dendritic cell progenitors give rise to myeloid ( monocytes and CD11c+DCs ) and lymphoid (CD11c-plasmacytoid DCs) precursors. Uponinteraction with inflamed endothelium, monocytes differentiate into CD11+blood DCs which give rise to langerhans cells, interstitial DCs, and macrophages. Differentiation of plasmacytoid DCs from CD34+progenitors can be blocked by Id2 and Id3 overexpression, suggesting their lymphoid origin.
DENDRITIC CELLS AND ANTI-CANCER THERAPY
Dendritic cells are potentially good candidates for immune-based therapies for a variety of reasons. In particular, the following aspects are important---
Their ability to migrate through tissues and infiltrate into tumours, where they encounter TAAgs which they capture, digest, and re-express for effective induction of a CMI response;
Their capacity to activate native T cells in regional lymph nodes and theirdifferentiation into CTLs, specifically able to interact with cancer cells and lead to tumour cell damage and death;and
Their role as APCs and capacity to process and present a spectrum of different Ags simultaneously that allows for the induction of a broad repertoire of anti-tumour immune responses to occur.
The ability of DCs to generate anti-tumour immune responses in vivo has been documented in a number of animal tumour models.Most of these experiments have involved in vitro isolation of DCs, followed by loading of the DCs with tumour Ags and injection of the Ag-bearing DCs into syngeneic animals as a cancer vaccine. Dendritic cells loaded with tumour lysates, tumour Ag-derived peptides, synthetic MHC class I-restricted peptides and whole proteins, have all been demonstrated to generate tumour-specific immune responses and anti-tumour activities. Furthermore, Ag-loaded DCs can be used therapeutically to induce regression of preexisting tumours. Dendritic cells loaded with appropriate TAAgs can induce either protection or rejection of malignant cells in various animal models.
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Read Full Article Below at it's Source.. Learn all you Can.. Make Your Own Decisions.
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Showing posts with label Dendritic Cell Therapy. Show all posts
Showing posts with label Dendritic Cell Therapy. Show all posts
11/15/08
CBS News Clip on the Breast Cancer Vaccine - Supposed Breaking News
A Few Insights on this “Experimenal Breast Cancer Vaccine” News Clip from last Thursday’s CBS News. The News Clip talked of a Vaccine for Breast Cancer, they spoke of this being a new “experimental” therapy to cure or at least prolong the survival rate of Breast Cancer. This sounds to me like “Dendritic Cell Therapy” which has been around for awhile, though main stream medicine has “harassed” those using this Cure successful for over a decade.
Those attempting to cure you naturally or using innovative means have long been kept down and shut up by the Medical Cartel, why ? Apparantly it has never been about you being healthy but instead about controlling you - keeping you down and making plenty of money in the mean time.
One wonders how money could possibly be worth your life, I mean it is only paper Really, however, beyond the piece paper, being in control of your life and your decisions seems to be very important to them. I want you to know more and to be able to make informed decisions on your own.
These courageous doctors have been making peoples lives better by healing their “total body”, stimulating their own immune system to not only cure their cancer but also heal many other ailments and health issues that they have. They do this by Using your Own Immune system to target the cancerous cells in your body. This can be done to target a specific tumor or a cancer, and can even be done in order to stimulate your immune system to Fix, Go After all that ails you, your body will simply know what to do.
These courageous doctors have been making peoples lives better by healing their “total body”, stimulating their own immune system to not only cure their cancer but also heal many other ailments and health issues that they have. They do this by Using your Own Immune system to target the cancerous cells in your body. This can be done to target a specific tumor or a cancer, and can even be done in order to stimulate your immune system to Fix, Go After all that ails you, your body will simply know what to do.
One Doctor I know of that does this type of therapy by Creating a Vaccine from your own cells, has been doing it successfully for10 years. The CBS report acts like it is new, it is NOT New. It has just been kept secret by the medical establishment. They keep secrets by the FDA and their thug like authority to "Jail People" who have and give the answers for your to be well.
Dendritic Cell Therapy, which uses a Vaccine to Heal Cancer and to stimulate your own cells to actually fight the bad guys, is a viable treatment option that really has been in use for quite awhile. So why is Main Stream Media now open to talking about this Vaccine?
From my Understand Dendritic Cell Therapy uses your own cells to formulate a vaccine to heal your cancer. This therapy is supposedly based on the principle of taking the cells from your body re-training these cells and re-entering the cells into your body
The Dendritic Cell therapy can be used to target a cancerous tumor by using cells of that tumor to be taken from your body and the Cells will then be “trained” to fight cancerous cells, all based on your own body, your unique chemical makeup.
For More Information On Dendritic Cell Therapy Click Here.
http://www.cancersolutions.org/search/label/Dendritic%20Cell%20Therapy
Main Stream Medical is testing this option and talking about it on the news as if it is Some Great New Breast Cancer Vaccine and Preventative, you will hear more about it, so be Cautious and NEVER accept One Source as your Answer. We will talk in later posts on how to know if the information you are finding about Natural Breast Cancer cures is right for you and if it has any truth to it. There is a whole lot of conflicting information online.
Remember For Every website talking about natural cancer cures there is information deliberately put on websites in order to make you think that the cure does not work or can harm you, more on that later.
If Main Stream Medical gets a hold of this Therapy and accepts this as a Viable Cancer though it has been in use a minimum of 10 years and has already been working my fear is that this “cure” will be controlled, changed, not work as well and will cost a whole lot more.
Dendritic Cell Therapy, which uses a Vaccine to Heal Cancer and to stimulate your own cells to actually fight the bad guys, is a viable treatment option that really has been in use for quite awhile. So why is Main Stream Media now open to talking about this Vaccine?
From my Understand Dendritic Cell Therapy uses your own cells to formulate a vaccine to heal your cancer. This therapy is supposedly based on the principle of taking the cells from your body re-training these cells and re-entering the cells into your body
The Dendritic Cell therapy can be used to target a cancerous tumor by using cells of that tumor to be taken from your body and the Cells will then be “trained” to fight cancerous cells, all based on your own body, your unique chemical makeup.
For More Information On Dendritic Cell Therapy Click Here.
http://www.cancersolutions.org/search/label/Dendritic%20Cell%20Therapy
Main Stream Medical is testing this option and talking about it on the news as if it is Some Great New Breast Cancer Vaccine and Preventative, you will hear more about it, so be Cautious and NEVER accept One Source as your Answer. We will talk in later posts on how to know if the information you are finding about Natural Breast Cancer cures is right for you and if it has any truth to it. There is a whole lot of conflicting information online.
Remember For Every website talking about natural cancer cures there is information deliberately put on websites in order to make you think that the cure does not work or can harm you, more on that later.
If Main Stream Medical gets a hold of this Therapy and accepts this as a Viable Cancer though it has been in use a minimum of 10 years and has already been working my fear is that this “cure” will be controlled, changed, not work as well and will cost a whole lot more.
However, with this your medical insurance may then pay for it, while now the medical insurance companies seem to only want you to do what your doctor says or they won’t pay. This way everyone gets paid in the system of getting you healthy. Whether their solution works or not is irrelevant, your pain level and health level is irrelevant. It is all about the numbers, the money, and your Real Health, gets lost in everyone else’s needs and agendas.
Why won't medical insurance Pay for PROVEN natural cures that are easier on your body and easier on your life? It is because Big Business supports Big Business, your Cancer pays a whole lot of wages, and they can charge VERY high prices if a Big insurance company is paying the bills, they are all interwined and your life is paying the Price.
The Message of this Post is though the Main Stream media seems to be talking about a Breast Cancer Vaccine, be cautious there is more then meets the eye. If they are now open to making this information public after all these years, then they must be in a position to Control the Information, Control the Vaccine and how it is administered
They talk about this vaccine maybe being a preventative. I believe this to be true in the aspect of using “Dendritic Cell Therapy” in order to boost your immune system and keep it strong enough to fight off cancer in the first place.
The Message of this Post is though the Main Stream media seems to be talking about a Breast Cancer Vaccine, be cautious there is more then meets the eye. If they are now open to making this information public after all these years, then they must be in a position to Control the Information, Control the Vaccine and how it is administered
They talk about this vaccine maybe being a preventative. I believe this to be true in the aspect of using “Dendritic Cell Therapy” in order to boost your immune system and keep it strong enough to fight off cancer in the first place.
However, if it is specifically targeted you would have to have the breast cancer, the health issue before your cells can be used to make a Vaccine just for you. If you are healthy and you make the vaccine, it is my understand that this would not necessarily work as a preventative.
I am not a Doctor, nor am I attempting to provide medical advice, I am an Alternative Medicine Researcher and I am passionate about your health.
Who will provide this “New” vaccine that has found it’s way into the Main Stream Media, no doubt a Big Pharma Company will be in charge of this. And will they will make Billions, for it works. Prescription drugs, in part are based on herbal remedies but because herbs cannot be “patented” they create their own drugs that they can patent.
I mean the Native Americans cured themself of Cancer, Societies LONG before us cured themselves of all kinds of human health issues. The ground Naturally grows what humans need to be well and yet some dark force uses those herbs mixed with man made filler and patents this cure to then sell it to you.
And these drugs just keep coming. Some have no reall cure in them, they are placebos and others are just to cause more problems so you buy more prescriptions. All based on Profits for Big Pharma Companies. The recent news had a special on the FACT that doctors Give YOU a placebo 50% of the time, so you are Tricked into thinking that they are making you better. The Power of Your Own Thoughts Heals you and they take the Credit and the Paycheck from giving you NOTHING...
These Companies are publicly traded and their whole purpose is making money. This kind of money is based on volume and is not about your health, it is not about your long term wellness or your comfort level with the whole process. Your Body, your life, and your quality of life is just a numbers game to them.
I want you to Be in Charged or Your Own Health, To make your own decisions.
Here is a Link to the Breast Cancer Vaccine Article, Click Here.
http://abcnews.go.com/Health/CuttingEdge/story?id=6247113&page=1
http://abcnews.go.com/Health/CuttingEdge/story?id=6247113&page=1
Who is In Charge of Your Breast Cancer Cure ?
11/13/08
ABC News - Cancer Vaccine
Tonight on ABC news they talked of a Vaccine for Breast Cancer, made from your own cells. WoW - it is being tested and well it may just work. Duh... I say What? I mean this is Dendric Cell Therapy, they are talking now because the public is demanding to know about cures that have been hidden. Chemo is Horrific and Outdated, it is NOT the only or best way, in my opinion to Cure Cancer.
This therapy has been around for quite awhile, the Doctors offering this therapy have been threatened, I guess so many doctors are doing it and patients are being "Spontaneously Cured" that the Real News must start talking about this therapy. Once the Main Stream starts doing this "Therapy" - "Cure" - "Vaccine" then it will most likely cost a HUGE amount more then it does now and it will Be Regulated most likely.
This therapy has been around for quite awhile, the Doctors offering this therapy have been threatened, I guess so many doctors are doing it and patients are being "Spontaneously Cured" that the Real News must start talking about this therapy. Once the Main Stream starts doing this "Therapy" - "Cure" - "Vaccine" then it will most likely cost a HUGE amount more then it does now and it will Be Regulated most likely.
I am Glad this is on the News, but I am Skeptical of the way they are presenting it.
10/29/08
Dendritic Cell Therapy - Science Blog
Dendritic cells help the body to switch on an immune response by seeking out foreign proteins (antigens) and showing them to the T and B cells. They are normally present all over the body but only in very small numbers, which means that they are difficult to isolate and study. At the British Society for Immunology Annual Congress in Brighton this week, Dr Jonathan Austyn of the University of Oxford will explain how recent advances have made it possible to grow large numbers of dendritic cells in the lab, opening the way to their use in the treatment of cancer.
However, immunologists now think it should be possible to over-ride the effects of these substances. Dendritic cells can be separated from the patient's blood or bone marrow and grown in large quantities in culture. They can then be shown bits of the tumour to which the immune system will react (tumour antigens) and reinfused into the patient. A recent clinical trial using this approach in the United States was most encouraging.
In certain types of cancer, such as the skin cancer malignant melanoma, it is known that patients can mount an immune response to the developing tumour. However, in many cases this response ultimately fails. Could treating patients with beefed-up dendritic cells help to maintain this response?
Dr Austyn and his colleagues will be starting a Phase I clinical trial early in 1998 where they will use dendritic cells to try to treat patients with advanced (Stage IV) malignant melanoma or breast cancer. The patients in the trial have not responded to conventional treatments and have metastatic skin lesions.
Dendritic cells from the patients' blood will be grown and induced to develop into their mature form in culture. They will then be injected directly into the skin lesions. The team hope that the mature dendritic cells will pick up tumour antigens and switch on an immune response.
One problem that Dr Austyn foresees is that patients with advanced cancer often have weakened immune systems. Therefore it is possible that even the most potent dendritic cells will not be able to switch on a strong enough immune response to totally eradicate cancers. However, Dr Austyn suggests that this problem may be overcome by using dendritic cells in conjunction with other types of immunotherapy.
Dendritic cell therapy alone may also prove useful for patients at high risk of recurrence after a primary tumour has been removed by surgery, or for healthy people at risk of developing familial types of cancer.
Notes:1. Dr Austyn is speaking in the Vaccines session on Thursday 4 December. The BSI 5th Annual Congress is at the Brighton Centre, Brighton, UK from 2-5 December 19972. Dr Austyn can be contacted at the Nuffield Department of Surgery, University of Oxford, The John Radcliffe Oxford Radcliffe Hospitals NHS Trust, Headington, Oxford OX3 9DU. Tel: +44 1 865 221 281 Fax: +44 1 865 768 876 jon.austyn@surgery.oxford.ac.uk3.
Cancers may develop because the immune system is not given a strong enough signal to destroy the tumour. There is even evidence that, in some cases, cancers are able to turn off the immune response. For example, immature dendritic cells are found in some cancers.
However, substances produced by the tumour prevent the cells from developing into a more mature form which can stimulate an immune response. These substances may even cause the death of the dendritic cells.
However, immunologists now think it should be possible to over-ride the effects of these substances. Dendritic cells can be separated from the patient's blood or bone marrow and grown in large quantities in culture. They can then be shown bits of the tumour to which the immune system will react (tumour antigens) and reinfused into the patient. A recent clinical trial using this approach in the United States was most encouraging.
In certain types of cancer, such as the skin cancer malignant melanoma, it is known that patients can mount an immune response to the developing tumour. However, in many cases this response ultimately fails. Could treating patients with beefed-up dendritic cells help to maintain this response?
Dr Austyn and his colleagues will be starting a Phase I clinical trial early in 1998 where they will use dendritic cells to try to treat patients with advanced (Stage IV) malignant melanoma or breast cancer. The patients in the trial have not responded to conventional treatments and have metastatic skin lesions.
Dendritic cells from the patients' blood will be grown and induced to develop into their mature form in culture. They will then be injected directly into the skin lesions. The team hope that the mature dendritic cells will pick up tumour antigens and switch on an immune response.
One problem that Dr Austyn foresees is that patients with advanced cancer often have weakened immune systems. Therefore it is possible that even the most potent dendritic cells will not be able to switch on a strong enough immune response to totally eradicate cancers. However, Dr Austyn suggests that this problem may be overcome by using dendritic cells in conjunction with other types of immunotherapy.
Dendritic cell therapy alone may also prove useful for patients at high risk of recurrence after a primary tumour has been removed by surgery, or for healthy people at risk of developing familial types of cancer.
Notes:1. Dr Austyn is speaking in the Vaccines session on Thursday 4 December. The BSI 5th Annual Congress is at the Brighton Centre, Brighton, UK from 2-5 December 19972. Dr Austyn can be contacted at the Nuffield Department of Surgery, University of Oxford, The John Radcliffe Oxford Radcliffe Hospitals NHS Trust, Headington, Oxford OX3 9DU. Tel: +44 1 865 221 281 Fax: +44 1 865 768 876 jon.austyn@surgery.oxford.ac.uk3.
There will be a press office at the meeting in operation from 9am on Tuesday2 December. Tel: +44 1 273 724 320 / 0378 406 416. Journalists are welcome to attend but are asked to contact Kirstie Urquhart in advance to register.4. Before the meeting Kirstie can be contacted on +44 181 875 2402 / kirstie@immunology.org
Dendritic Cell Therapy for Breast Cancer
Initial Award Abstract (1997)In this project, we intend to test whether normal cells from the blood stream of breast cancer patients called dendritic cells have the ability to stimulate immunity against breast cancer.
The dendritic cells are normally present in small numbers in the blood, and stimulate immunity very strongly against viruses, bacteria, cancer cells and other foreign invaders. Scientists have developed a way to grow these cells in large numbers outside the body within a week after removing a sample of blood and exposing the white blood cells to growth factors that encourage the growth of dendritic cells. In this research project, dendritic cells will then be exposed to a synthetic piece of a substance present on breast cancer cells called "CEA" that is present on tumors from two thirds of patients with breast cancer.
Dendritic cells will be grown for a week outside the body and then exposed to a fragment of the "CEA", followed by infusion in large numbers into the veins of patients with breast cancer that has spread widely and cannot be cured with chemotherapy, radiation or surgery.
Increasing doses of the cells will be given to groups of at least three patients with breast cancer in order to find out whether the dendritic cells cause side effects when given twice over a period of two weeks.
Stimulation of the immune system against breast cancer will be measured before and after the dendritic cells are given by removing a sample of blood for analysis in the laboratory and by other tests. Shrinkage of tumor will also be measured.
In this 2 year trial of 24 patients with metastatic breast cancer, we will ask whether patients that receive CEA dendritic cells can increase their immunity against breast cancer without side effects, and whether increased immunity against breast cancer can cause shrinkage of tumors.
The long term goal of this initial study is to find ways to educate the immune system to recognize and destroy breast cancer cells even though the presence of the tumor and the chemotherapy agents used to shrink the breast cancer have caused decreased levels of immunity.
The results of this initial CEA dendritic cell study will determine the course of future studies depending on whether shrinkage of tumor is seen, in which case a follow-up study will be performed to confirm that CEA dendritic cells are effective for the treatment of metastatic breast cancer.
If no tumor shrinkage is seen, but immunity against breast cancer is boosted, then patients will be treated with CEA dendritic cells and then have a blood sample removed to try to grow another type of white blood cell called killer T cells that can be directed against breast cancer.
This use of dendritic cells to stimulate immunity against breast cancer is supported by work showing that in the mouse and in humans, dendritic cells are the strongest stimulators of the immune system. This immunologic approach to breast cancer is an attempt to harness the body’s natural defenses to eliminate tumors by boosting the immune response directed against a substance found on cancer cells.
Final Report (1999)In our proposal, entitled "Peptide pulsed Dendritic Cell Therapy for Breast Cancer," we had two specific aims: the first aim was to perform a clinical trial in which patients whose tumors over had the tumor marker CEA were treated with their own dendritic cells, which are immune stimulating cells from the bloodstream, to which a fragment (a peptide) of the CEA marker protein was added.
The goals of the trial were to determine what side effects the dendritic cell therapy caused and to measure whether tumors shrank after treatment with CEA peptide pulsed dendritic cells. In the second specific aim we wished to measure whether the injection of dendritic cells that were pulsed with the CEA peptide caused a boosting of immunity in patients.
The results of our study are that generation of dendritic cells from patients with breast cancer that have been heavily pre treated with chemotherapy was difficult, with low yields.
The resulting dendritic cells had less of the cell surface molecules than dendritic cells from non-chemotherapy treated patients with metastatic melanoma, for example. We were able to infuse cells in 16 patients, but found that there was no evidence of tumor shrinkage in any patient. Immunologic assays revealed that the CEA peptide pulsed dendritic cells did not result in boosting of immunity in general or specifically directed against the CEA antigen with which the dendritic cells were pulsed.
This information leads us to believe that in a population of breast cancer patients that were heavily pre treated with chemotherapy, the CAP 1 CEA peptide loaded onto dendritic cells was not capable of provoking an immune response and did not cause tumors to shrink. Newer peptides that have been produced synthetically are being developed that bind more strongly to the dendritic cells and may be more capable of causing immune recognition of tumor cells.
In addition, we believe that patients that have not been previously treated with chemotherapy and have minimal disease burden are ideal candidates for dendritic cell treatment in future trials.
http://www.cbcrp.org/research/PageGrant.asp?grant_id=154
The dendritic cells are normally present in small numbers in the blood, and stimulate immunity very strongly against viruses, bacteria, cancer cells and other foreign invaders. Scientists have developed a way to grow these cells in large numbers outside the body within a week after removing a sample of blood and exposing the white blood cells to growth factors that encourage the growth of dendritic cells. In this research project, dendritic cells will then be exposed to a synthetic piece of a substance present on breast cancer cells called "CEA" that is present on tumors from two thirds of patients with breast cancer.
Dendritic cells will be grown for a week outside the body and then exposed to a fragment of the "CEA", followed by infusion in large numbers into the veins of patients with breast cancer that has spread widely and cannot be cured with chemotherapy, radiation or surgery.
Increasing doses of the cells will be given to groups of at least three patients with breast cancer in order to find out whether the dendritic cells cause side effects when given twice over a period of two weeks.
Stimulation of the immune system against breast cancer will be measured before and after the dendritic cells are given by removing a sample of blood for analysis in the laboratory and by other tests. Shrinkage of tumor will also be measured.
In this 2 year trial of 24 patients with metastatic breast cancer, we will ask whether patients that receive CEA dendritic cells can increase their immunity against breast cancer without side effects, and whether increased immunity against breast cancer can cause shrinkage of tumors.
The long term goal of this initial study is to find ways to educate the immune system to recognize and destroy breast cancer cells even though the presence of the tumor and the chemotherapy agents used to shrink the breast cancer have caused decreased levels of immunity.
The results of this initial CEA dendritic cell study will determine the course of future studies depending on whether shrinkage of tumor is seen, in which case a follow-up study will be performed to confirm that CEA dendritic cells are effective for the treatment of metastatic breast cancer.
If no tumor shrinkage is seen, but immunity against breast cancer is boosted, then patients will be treated with CEA dendritic cells and then have a blood sample removed to try to grow another type of white blood cell called killer T cells that can be directed against breast cancer.
This use of dendritic cells to stimulate immunity against breast cancer is supported by work showing that in the mouse and in humans, dendritic cells are the strongest stimulators of the immune system. This immunologic approach to breast cancer is an attempt to harness the body’s natural defenses to eliminate tumors by boosting the immune response directed against a substance found on cancer cells.
Final Report (1999)In our proposal, entitled "Peptide pulsed Dendritic Cell Therapy for Breast Cancer," we had two specific aims: the first aim was to perform a clinical trial in which patients whose tumors over had the tumor marker CEA were treated with their own dendritic cells, which are immune stimulating cells from the bloodstream, to which a fragment (a peptide) of the CEA marker protein was added.
The goals of the trial were to determine what side effects the dendritic cell therapy caused and to measure whether tumors shrank after treatment with CEA peptide pulsed dendritic cells. In the second specific aim we wished to measure whether the injection of dendritic cells that were pulsed with the CEA peptide caused a boosting of immunity in patients.
The results of our study are that generation of dendritic cells from patients with breast cancer that have been heavily pre treated with chemotherapy was difficult, with low yields.
The resulting dendritic cells had less of the cell surface molecules than dendritic cells from non-chemotherapy treated patients with metastatic melanoma, for example. We were able to infuse cells in 16 patients, but found that there was no evidence of tumor shrinkage in any patient. Immunologic assays revealed that the CEA peptide pulsed dendritic cells did not result in boosting of immunity in general or specifically directed against the CEA antigen with which the dendritic cells were pulsed.
This information leads us to believe that in a population of breast cancer patients that were heavily pre treated with chemotherapy, the CAP 1 CEA peptide loaded onto dendritic cells was not capable of provoking an immune response and did not cause tumors to shrink. Newer peptides that have been produced synthetically are being developed that bind more strongly to the dendritic cells and may be more capable of causing immune recognition of tumor cells.
In addition, we believe that patients that have not been previously treated with chemotherapy and have minimal disease burden are ideal candidates for dendritic cell treatment in future trials.
http://www.cbcrp.org/research/PageGrant.asp?grant_id=154
Dendritic Cell Therapy Article
There are many hundreds of papers on dendritic cell therapy vaccines in the medical literature. The numbers are increasing all the time.
Also the cancers involved are extending.
The first dendritic cell therapy vaccines were used in melanoma, which is a highly immunogenic tumour. Following that, there has been a range of papers on kidney cancers, prostate cancer, brain tumours, bowel cancers and on and on.
These approaches have been mostly used in Stage 3 and 4 cancers and have gone through Phase 2 clinical trials and some have gone through Phase 3 clinical trials.
Dendritic Cell Therapy Stanford Article
Since then, a larger number of patients with non-Hodgkin's lymphoma have been treated at Stanford with idiotype-pulsed DCs and the efficacy confirmed. In addition, pilot clinical trials of antigen-pulsed DCs have been conducted at Stanford in various types of cancer, including prostate cancer, colorectal cancer, multiple myeloma, and non-small cell lung cancer. These studies, and other studies carried out elsewhere, show that antigen-loaded DC vaccinations represent a safe and promising form of immunotherapy for a wide range of malignancies.
Dendritic Cell Therapy
The Immune System
The immune system is the body's defense system. It works on three different levels. The first level is the anatomic response. It consists of anatomical barriers to foreign particles and includes the skin and acid in the stomach. Anatomic barriers prevent foreign substances from entering the body. If foreign particles pass through the first line of defense the second line of defense called the inflammatory response kicks in. The third line of defense is the immune response. It is the main player in specific immune defense.
The cells of the immune system mount the immune response.
These cells are also called white blood cells.
Another Useful Link
Dendritic cells drawn from a sample of the patient's blood are ....
Atricle on Brain Cancer, Dendritic Cell Therapy ...
http://www.mycentraljersey.com/article/20081021/HEALTH/810210311/-1/newsfront
Dendritic cells drawn from a sample of the patient's blood are exposed in a lab dish to the biomarkers of the patient's own tumor, then activated and "educated." These cells then are injected back into the patient and mobilize the immune system to recognize and attack the cancer.
The early results are stunning: It appears as if the vaccine increases survival by as much as 50 percent, according to the Brain Tumor Center of New Jersey. That's music to Montag's ears.
"I could feel the difference, physically," said Montag, who after Labor Day received approval from her surgeon, Dr. Brian Beyerl, to return to work for 15 hours per week. "I just felt better, stronger. I am doing desk work and reviewing charts, but it is exciting to be back."
Charlene Ruggiero, one of Montag's colleagues at Overlook, admires Montag's courage and says Montag provides an example for any brain cancer patients to follow.
"Her optimism, strength and caring nature, in addition to being a nurse in the same shoes as her patients, means the world to them," Ruggiero said. "She offers them something no one else can: tangible hope."
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