Prostate Cancer Treatment Utilizing Immunotherapy

In the June 2005 Townsend Letter, Dr. Ralph Moss profiled the newest treatment for prostate cancer, Provenge, which is manufactured by Dendreon Corporation of Seattle. Provenge is an autologous vaccine made by initially separating out antigen-presenting cells, namely dendritic cells and macrophages, 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 called GM-CSF, and this mixture is introduced to the isolated antigen-presenting cells. While the results of the study found that those men on the Provenge treatment regimen lived longer, the progression of disease in these men was not delayed.

Does this Sound familiar?

Dendritic cell therapies have been offered in some format or another for years now. The reason for utilizing dendritic cells as an Immunotherapy is a sound one, considering that dendritic cells are the absolute best cell in the body at delivering antigen to lymphocytes that can actually recognize tumors as being foreign and mediate some type of anti-tumor response. In the past, 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 these enhancements is the same in all cases: to improve the chance that a T lymphocyte will get the signal from the dendritic cell and begin 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 worse yet, that their 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 sometimes shed their tumor antigens and therefore evade the immune system? Is the hope that a dendritic cell will actually find a functional T lymphocyte really the pinnacle of cancer immunotherapy?

The major limitations of dendritic cell therapy include the dependence on T lymphocyte numbers and functionality, and the fact that the large 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, who say we can't take a shortcut? That is, why not simply proliferate, outside the body, large numbers of lymphocytes with anti-tumor activity for therapeutic use? This would seem to take the guesswork out of the process of using dendritic cells. This approach has actually been in the works for decades, pioneered chiefly by Dr. Steven Rosenberg of the National Cancer Institute. In an October 2004 publication, Rosenberg and colleagues detailed the results 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 large numbers of antigen-specific lymphocytes. These cells were then reinfused into the patient's, with promising results: 18 of 35 patients receiving the lymphocyte treatment experienced at least a 50% regression of their tumor.

Clearly this approach warrants further research and refinement, due to its potential as an effective, non-toxic cancer treatment. One limitation of this approach is that it is dependent 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 is extremely promising.

Not Restricting Your 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 over the last 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 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 seen in these cases. The results of these trials have been encouraging, with multiple clinical remissions seen in each one, and further research is already underway. The advantages of using NKs for immunotherapy go beyond their innate ability to destroy tumor cells. NKs can be expanded in the laboratory, and can be achieved in substantial numbers from white blood cell fractions from 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 noted that in our endeavors of culturing NKs for therapeutic use, we are also expanding NK T cells, cytotoxic T lymphocytes, and to a small 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. In fact you get both antigen specific and Non.

Envita is Leading the Way in Immunotherapy Cancer Treatment

As NK immunotherapy treatments have moved forward countless improvements have been made, and solved, and researchers will hone their skills and knowledge in dealing with specific types of cancers and specific immune system issues found in individual cancer patient. Science has never been nearer to harnessing 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 so many years, attempting to find that magical combination of immune components that can dissipate established cancers in the body. Their successes are the building blocks for the future of non-toxic, natural cancer treatments. Envita's International Cancer Center is leading the Way. Our AAIT is a powerful proprietary Treatment for cancer, this treatment not available in our US centers but in our Mexico Center.