Dr. Ralph Moss profiled the most current treatment for prostate cancer, referenced in the June 2005 Townsend Letter, Provenge, manufactured by Dendreon Corporation of Seattle. Provenge is primarily an autologous vaccine composed by initially separating out antigen-presenting cells, namely dendritic cells and macrophages, secreted from a patient's blood. Following isolation of these cells a protein called PAP, or prostatic acid phosphatase, is fused with an immune-stimulating cytokine, identified as GM-CSF. Subsequently, this mixture is introduced to the isolated antigen-presenting cells. While the positive results of the study indicated that those men on the Provenge treatment regimen survived longer, the progression of disease in these patients was not delayed.
Sound somewhat familiar? Dendritic cell therapies have been proposed in some format or another for quite a number of years now. The impetus for utilizing dendritic cells as an immunotherapy is valid, considering that dendritic cells are undeniably the foremost cells in the body poised to deliver antigen to lymphocytes that can actually recognize tumors as being foreign and mediate some type of anti-tumor response. Historically, dendritic cells have been genetically modified to secrete immune-stimulating cytokines, transfected with multiple antigens, and even electroporated to ensure that the target antigen is actually being processed for antigen delivery. The reason for such enhancements is identical in all cases: to improve the odds that a T lymphocyte will receive the signal from the dendritic cell and initiate an immune response.
What Can Go Wrong In Dendritic Cell Cancer Treatment
So what if a cancer patient has a low number of lymphocytes, or considerably worse, that his lymphocytes simply will not respond to the tumor even after the dendritic cell has presented the antigen to it? What about metastatic tumor cells, which can occasionally shed their tumor antigens and therefore evade the immune system? Is the expectation that a dendritic cell will actually find a functional T lymphocyte truly the pinnacle of cancer immunotherapy?
The major limitations of dendritic cell therapy include the dependence on T lymphocyte quantities and functionality, and the fact that the immense numbers of dendritic cells necessary to mount an effective anti-tumor immune response can only be obtained as precursor monocytes and macrophages through leukaphoresis. Dendritic cells constitute only about 1% of leukocytes in the body at any given time, and are found in greater abundance in the skin than in the peripheral blood.
So, if the goal of dendritic cell therapy is to elicit a specific immune response from a T lymphocyte, why can't we take a shortcut? Pointedly, why not simply proliferate, outside the body, large numbers of lymphocytes with anti-tumor activity for therapeutic use? This would seem to eliminate the guesswork regarding use of dendritic cells. This approach has actually been warranted for decades, pioneered chiefly by Dr. Steven Rosenberg of the National Cancer Institute. In an October 2004 publication, Rosenberg and colleagues detailed the findings of a clinical trial using anti-tumor lymphocytes in melanoma patients whose disease had become refractory to treatment. For each patient, tumor-infiltrating lymphocytes were isolated from tumor samples, tested for their ability to recognize tumor cells in the laboratory, and then expanded over the course of 2-3 weeks to generate massive numbers of antigen-specific lymphocytes. These cells were then re-infused into the patient, with rather promising results: 18 of 35 patients receiving the lymphocyte treatment experienced at least a 50% regression of their tumor.
Clearly this approach merits further research and refinement, due to its potential as an effective, non-toxic cancer treatment. One limitation of this approach is dependence on the isolation of specific lymphocytes from a tumor sample, which can only be obtained by invasive procedures. Additionally, tumors that have down-regulated HLA expression will likely not be recognized by antigen-specific lymphocytes. Despite this, the treatment harbors profound promise.
Bolstering the Immune System, A Better Approach
Natural killer cells (NKs) are a key component of the innate immune response, and their ability to recognize virally-infected cells and tumor cells has been well-documented well over two decades. Unlike antigen-specific T lymphocytes, the cytotoxic abilities of NKs are not restricted to MHC recognition; even metastatic cells, which often evade immune recognition because they have down-regulated HLA expression, can essentially be targeted for destruction by NKs. Several clinical trials are currently underway using NK cell infusions, including some leukemia trials in which donor NKs are deliberately mismatched for HLA with the recipient, in order to create a graft-versus-leukemia response similar to the graft-versus-host response that can be observed in these cases. The results of these trials have been encouraging, with multiple clinical remissions evidenced in each, and further research is presently underway. The advantages of using NKs for immunotherapy go beyond their innate ability to eradicate tumor cells. NKs can be expanded in the laboratory, and can harvested in substantial numbers from white blood cell fractions in peripheral blood, without the need to isolate certain types of lymphocytes as starting materials. They can also be expanded without the use of tumor antigen, obviating the need to obtain tumor samples and minimizing the risk of cultivating auto-reactive lymphocytes. It should be emphasized that in our endeavor to culture NKs for therapeutic use, we are also expanding NK T cells, cytotoxic T lymphocytes, and to a lessor degree helper T cells. Rather than shifting the burden of tumor control to one type of effector cell, our treatment multiplies all the lymphocyte subsets that have anti-tumor activity, therefore directing a more balanced attack from the patient's own immune system.
Envita Leading the Way in Immunotherapy Cancer Treatment
As NK immunotherapy treatments have progressed countless improvements have been initiated, obstacles resolved, as researchers effectively hone their skills and knowledge while dealing with specific types of cancers and specific immune system issues found in individual cancer patients. Science has never been better equipped to harness the full potential of the immune system for the treatment of cancer than it is today. The number of prestigious institutions performing clinical trials with NK immunotherapy is a testament to all those who have labored in this realm for decades attempting to ascertain that magical combination of immune components that can dissipate established cancers in the body. Their triumphs are the building blocks for the future of non-toxic, natural cancer treatments. Envita International Cancer Center is leading the way. Envita AAIT is powerful proprietary treatment for cancer. Such treatment not yet available in our US centers but can be incorporated in our Mexico Center.
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