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Limitations of Current Immunotherapies
Currently, the most common forms of immunotherapy are mAbs (monoclonal antibodies), which are commercially available, and cancer vaccines, with the first approved cancer vaccine, Provenge, for prostate cancer. Provenge is the first immunotherapy success story that has reached commercialization.
Provenge is an autologous cancer vaccine and works by stimulating the patient’s own immune system to target prostate cancer cells. The process of making Provenge involves the introduction of a patient’s immune cells to a protein that functions as a prostate-cancer associated antigen. An antigen is a substance that causes the body to mount an immune response to the specific antigen (usually a peptide or a protein). This process activates the patient’s own immune cells against prostate cancer cells, which express the same antigen(s) to help the immune system better fight the disease.
Provenge represents a huge success and has shown great results, however, it is very hard to produce in large quantities. It is an autologous vaccine, meaning one patient one vaccine (prepared from the patient’s own cancer cells), which does readily not lend itself to commercial scale production and world-wide distribution.
Most of the other immunotherapies have been designed to be ‘targeted’ to specific antigens on cancer cells. As a result of the interaction of the targeted antigen with the passively administered mAb or the antibody produced by the body in response to the vaccine, a cascade of events leads to tumor cell death.
Targeted cancer immunotherapies, like monoclonal antibodies and certain vaccines, are aimed at finding a “magic bullet” - a cancer treatment which can destroy only the cancer cells and spare the healthy cells.
This approach has not been as successful as expected. After global efforts and more than 40 years of work in the fight against cancer, the “magic bullet” has not been found using targeted therapies. The hope for a “magic bullet”, not surprisingly, proved unfounded considering the complexity of a disease such as cancer. In addition, the products were not always as pure or specific as they were initially thought to be and were generally more toxic when given systemically, especially when given in high doses.
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The major problem with targeted therapies: they are “too targeted”; the targets are different among different patients, and the targets change when cancer cells mutate; |
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Not all antigens are the same; All cancers may “look” the same, but they are not. Not all patients’ cancers may express the antigen against which a specific monoclonal antibody or cancer vaccine is targeted. Response rates in general to “targeted therapies” appear to be around 20 to 30 percent. To optimize this type of therapy it will be necessary to identify each subgroup of patients with a specific cancer and develop therapies targeted to, or directed specifically at, their individual cancers. This approach, while scientifically attractive, is rather impractical and likely very expensive. |
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Tumor cells mutate as a result of chemotherapy and radiation treatment, and therefore, the target antigens on the tumor cells at which the therapy is aimed also change. If the target changes, then the mAbs or cancer vaccines which target those specific antigens become ineffective. |
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The second major problem with current immunotherapies is that they are administered to patients late in the cancer therapy cycle, when the patient’s immune system is already weakened. |
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Most immunotherapies have historically been used late in the disease treatment process after radiation, chemotherapy, or surgery (i.e. standard cancer therapy). This means they are typically used in cancer patients after the patient’s own immune system is weakened by initial standard cancer therapy. Often, they are used too late in the disease process to be effective. |
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Experts have now come to recognize that in order to achieve a meaningful immunotherapeutic effect when treating cancer, immunotherapy should be used as treatment early in the disease process. It should be used before the immune system is further weakened by radiation, chemotherapy and surgery, and before the cancer has become tolerated by the affected individual’s immune system. |
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