[gdpawel]

Tumor cell evolution enables cancer cells to evade destruction by the immune system. Cells that can be destroyed are destroyed. What is left is resistant to immune destruction. The mechanisms of escape are extremely diverse.

Tumor cells can lose the antigens (a molecule that the immune system reacts against and attacks) that trigger an immune response. In addition, tumor cells can inhibit the immune response, or develop resistance to the killing mechanisms involved.

For a tumor to grow and cause disease in the first place, it must evade destruction bv the immune system. The immune response is therefore a major selective pressure that directs the flow of tumor cell evolution.

This is one reason that immunotherapy has had so little success in the cure or chronic control of cancer in patients.

Tumor cells evolve that not only escape destruction by immune attack, but also that subvert normal immune cells to enhance tumor growth. Tumors recruit normal white blood cells to help in the process of tissue invasion.

Tumors also can release soluble factors that stimulate normal cells to produce enzymes that digest connective tissue and facilitate invasiveness. It's like renting bulldozers to clear space for new apartment houses.

The limitations of narrowly targeted therapy are also seen with cancer vaccines and immunotherapy. The earliest approaches at targeting tumor-specific molecules involved attempts to turn the immune system against proteins that are unique to cancer cells.

Certain types of lymphoma have a unique, patient-specific antibody on the surface of the lymphoma cells. The lymphoma cells make this antibody, which is absent from normal cells. Patients have been treated with antibodies targeted to the particular antibody on their lymphoma cells.

This antibody-against-an-antibody was prepared specially for each patient. In a study of 45 patients, eight responded. Only six patients had long-term control of their disease. The problem is that lymphoma cells can and do evolve without the surface antibody marker (Blood. 1998 Aug 15;92(4):1184-90).

Dr. Steven A. Rosenberg, Chief of Surgery at the National Cancer Institute (NCI) and a leading cancer immunologist, published a review of clinical trials on cancer vaccines. His analysis revealed that the overall response rate among 765 patients in a large number of different trials was only 3% (Nat Med. 2004 Sep;10(9):909-15).

Reference: "Cure: Scientific, Social and Organizational Requirements for the Specific Cure of Cancer" A. Glazier, et al. 2005