There are two general approaches to antiangiogenetic therapy. One is to block these growth factors; there are several such blocking agents, such as Avastin, being developed by various drug companies. They are in clinical trial and show promise, and also promise to be expensive if and when available. Further, as with many new drugs, adverse effects are being found, which may not outweigh their potential in cancer therapy. These drugs are currently for clinical trial only, and access requires participation in such trials.

A second approach is to deny a tumor the one component absolutely required for blood vessel growth - copper. Tumors hoard copper containing about three times the normal tissue levels of this mineral. Normal tissue function remains intact when the copper levels are only lowered but a tumor’s abnormal needs are  denied. Unlike the first approach , there is already a drug available. An agent with orphan drug status for the treatment of Wilson’s disease is available and works by decreasing body copper levels. Tetrathiomolybdate (TM) selectively chelates copper and has been safely used for many years in the treatment of Wilson’s disease. Initial studies indicate that it can decrease cancer cell growth. There are at least nine clinical trials of TM in progress, and these trials will attempt to prove activity in several cancer types. 

Tetrathiomolybdate treatment requires a month or more to reduce copper levels; then the patient must be maintained at this low copper level for several months. As with all cancer treatment, the sooner treatment starts the more likely there will be success. The treatment procedure is rigorous with regard to dosage timing, diet, and other restrictions. This is not a treatment to be individually undertaken. We cannot over stress the absolute need for patients using TM therapy to be in the care of a physician and be continually monitored for the duration of the treatment. Drug adjustments will likely be required over time to maintain the desired effect. As adjuvants to TM treatment, both vitamin C and zinc,if taken with meals, will decrease copper uptake. 

We feel that TM will become a major component of successful cancer therapy in both conventional and alternative  medicine. However, we also feel that TM’s potential will only be realized when TM is rationally combined  with other modalities, both while copper levels are being lowered, and later when the low copper level is being maintained. Time is never on the side of the cancer patient. If cancer growth can be slowed or halted, this offers more time as well as opportunity for other therapies to actually kill the cancer. We feel that immune therapy will be greatly improved when combined with antiangiogenesis. It is also likely that some alternative treatments will show sufficient activity under these conditions to demand they be recognized.

Natural Killer Cells and Cellular Immunobiology

Proponents of immune treatments for cancer have long anticipated the increased use of cellular immune therapy. The ability to use cellular immune components to directly attack the cancer cell is what immune therapy is about. The current treatments indirectly approach this by correcting immune imbalance and stimulating the immune system to produce those cellular components which attack cancer, such as T-cells, macrophages, etc. Actually giving the patient T-cells from an outside source is a major goal of emerging immune therapy.

This concept is not new.  It has had to await refinements and control which is now becoming possible. In the 1980s Rosenberg did pioneer studies with lymphocytes, removing them from patients, activating them and returning them to the patients, the so-called LAK cell (Lymphocyte Activated Killer cell). It is a useful treatment, though sometimes unreliable and ineffective. Newer refinements have greatly improved the treatment since Rosenberg, but it still does not give the degree of activity that we expect from immune therapy.

Dendritic cells are another approach which has shown some success, but not to the degree we know should be possible. Dendritic cells recognize cancer cells and take that information to the immune system stimulating the production of tumor specific T-cells (cytotoxic T-cells), which in turn attack the cancer cells. Dendritic cells can be cultured from the patient’s blood, grown in tissue culture and activated with cancer antigens.  When they are then reintroduced into the patient they can elicit an augmented immune response to the cancer. Dendritic cells from tissue culture do not produce as robust a response as native cells, indicating an area for improvement. Dendritic cells are also proving to be major adjuvants in cancer vaccine research.

Natural killer cells (NK cells) are a type of cytotoxic T-cell that are not specific for one cancer cell type, as are the tumor specific cells produced in response to dendritic cells. Originally NK cells were thought to simply attack cancer cells when they find them and not require activation by finding a specific cancer cell marker, hence the name natural killer cells. We now know that they are activated by lack of a cell marker that identifies the cell as “self” that is normal to the body. They are also activated by interleukin-2 and recent research has identified other activating factors. NK cell are considered to be an initial line of defense while the immune system makes tumor specific T-cells. However, due to the intensity of NK cell attack, they are receiving interest as the most promising of immune cell therapies. NK cells grown in tissue culture do not exhibit the decreased activity as tissue culture dendritic cells. Some research groups claim to have methods of further activating NK cells before reintroducing them into patients.

Recent reports of complete remissions of some cancers with NK cells has fueled the public’s interest in NK cells and generated over optimism for the treatment. Will all patients receiving NK cell therapy have a complete remission? Not in the near future. Will NK cell therapy become a major breakthrough in cancer? We believe this to be the case.

At present both dendritic and NK cell therapy offers promise, with NK cell currently having some advantage. Here at the Immune Recovery Centers of America we believe that a combined approach with both cellular therapies merits consideration. As the IRCs have found with other immune therapies, combined therapies in the proper sequence can improve response. We also believe that immune reconstitution before NK or dendritic cell therapy will enhance the ability of the immune system to maintain the NK and/or dendritic cell effect. Unfortunately such treatments in the US are classified as “clinical research” leaving patients with little option other than to go offshore. The Immune Recovery Centers maintain contact with groups researching cellular immunotherapy, and is developing strategic alliances with several laboratories to allow our patients access to such therapies. Because cellular immunotherapy offers such promise for cancer patients and is an intense area of research, we feel that treatment standards will develop which will allow more routine use in the US.