What if, rather than receiving one-size-fits all anticancer drugs, patients were treated with specially formulated treatments made to target their own cancer cells? What if patient’s own cancer and immune cells were actually used to develop a treatment just for their cancer?
Instead of suffering the side effects of cancer therapy that damage normal, healthy cells in addition to destroying cancer, patients may find that their own, personalized treatment is accompanied by relatively few discomforts. And, in place of the toxicity of conventional cancer treatment, their personalized therapy would stimulate their own immune system to attack cancer.
These concepts sound both far-fetched and compelling. In fact, personalized medicine has already impacted cancer treatment in the form of targeted therapy—treatment directed toward cancers that display certain markers on their surface. Examples are tamoxifen, a treatment for breast cancer that works to prevent breast cancer recurrence in the treatment of cancers that display the estrogen receptor on their surface. Also, Herceptin targets breast cancers that display the HER2-neu protein on their surface.
Personalized Medicine’s Quest to Utilize the Patients’ Own Immune System
Stimulating the immune system to attack unwanted substances is not a new concept; vaccines, which have traditionally been used to prevent infectious diseases such as measles and the flu, work in this way. What is new, however, is applying this idea to cancer treatment with the development of immunotherapies, or treatments that stimulate the immune system to attack cancer.
Cancer cells are formerly normal cells that have gone awry. However, the immune system—the body’s natural defense against disease—does not distinguish cancer cells from normal cells. This is why cancer is allowed to grow; the immune system does not attack cancer cells because it fails to recognize them as foreign and harmful.
The goal of immunotherapy is to help the body to recognize cancer cells as a threat and activate immune cells to attack the cancer. This is accomplished by working with the normal mechanisms of the immune system that allows it to recognize and target foreign invaders, such as viruses. For this reason, cancer immunotherapies may also be called cancer vaccines.
Antigens Are the Key
All cells have unique proteins or bits of protein on their surface called antigens. Many types of cancer have specific antigens that are present in abundance on their cell surface, which distinguishes them from normal cells. Immunotherapies work in two ways: First, they alert the immune system that cancer-specific antigens—or antigens that are abundantly present on cancer cells—are foreign. Second, immunotherapise stimulate the immune cells to attack cells that have these antigens on their surface.
Immunotherapies in Development
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There has been much progress in recent years in developing vaccines for the treatment of cancer. While none have been approved by the U.S. Food and Drug Administration (FDA) at this time, several strategies have shown promising results.
Provenge®: The immunotherapy Provenge is being developed for the treatment of prostate cancer. The prostate gland is part of the male reproductive system that produces some of the fluid for transporting sperm during ejaculation. Provenge utilizes the patient’s own immune cells, called dendritic cells, plus an antigen that is present on most types of prostate cancer. Two large clinical trials have shown that Provenge increases survival in the treatment of men with hormone-refractory, metastatic prostate cancer, a difficult to treat cancer that no longer responds hormonal therapy. , Provenge has been granted fast-track status by the FDA. This means that it has demonstrated the potential to address an unmet medical need for the treatment of a serious or life-threatening conditions; the FDA will expedite review of the license application.
Oncophage: According to results from a recent phase III clinical trial, the cancer vaccine Oncophage® (vitespen, formerly HSPCC-96) improves survival by over 50 percent in some patients with metastatic melanoma. Melanoma is a type of skin cancer that often starts as a mole. Although melanoma is very curable in its earliest stages prior to spreading, advanced-stage melanoma—which has spread to several distant sites in the body—is considered difficult to cure. Oncophage is a vaccine that is composed of components of the patient’s own cancer cells and stimulates the patient’s immune system to attack the cancer. This is the first vaccine that has been shown to help patients with this difficult to treat disease survive longer. Oncophage is in the last phase of clinical trials prior to FDA review. It has been granted orphan-drug status by the FDA.
E75 vaccine: A cancer vaccine that is made up of a part of the HER2/neu protein called the E75 peptide has been shown to reduce the risk of breast cancer recurrence by half compared to patients who received a placebo. The E75 vaccine helps the body recognize HER2/neu as a marker for cancer and stimulates the immune system to attack cells displaying this protein. It is administered in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), a growth factor that is naturally produced by the body and stimulates the production of more white blood cells, especially the two types called granulocytes and macrophages that are involved in immune response.
NSCLC vaccine: A cancer vaccine has also been shown to improve survival of patients with stage IIIB NSCLC. The goal of this vaccine (called L-BL25) is to produce an immune response against cells that express the antigen MUC1, which is widely and abnormally expressed on NSCLC cells. Results indicate that patients who were treated with the vaccine survived more than 4 months longer than the patients who received best supportive care. While this difference was not “statistically significant”, which means the difference may be attributable to chance, additional data suggests that the treatment provided a benefit. Patients with stage IIIB NSCLC who were treated with the vaccine survived twice as long as patients with the same diagnosis that received best supportive care. This vaccine is still in the very early stages of research, but the results appear promising.
Small EJ, SchellhammerPF, Higano CS, et al. Results of a placebo-controlled phase III trial of immunotherapy with APC801 for patients with hormone refractory prostate cancer (HRPC). Proceedings of the 41st Annual Meeting of the American Society of Clinical Oncology; Abstract #4500.Higano CS, Burch PA, Small EJ, et al. Immunotherapy (APC8015) for androgen independent prostate cancer (AIPC): final progression and survival data from a second Phase 3 trial. ECCO 13: The European Cancer Conference. European Journal of Cancer Supplements. 2005;3(4):1.
Antigenics. Antigenics Announces Preliminary Survival Data From Its Randomized Phase 3 Metastatic Melanoma Trial. Available at: http://www.antigenics.com/news/2005/1010.phtml. Accessed October 2005
Peoples GE, Burney JM, Hueman MT et al. Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients. Journal of Clinical Oncology. Early online publication September 12, 2005.
Murray N, Butts C, Maksymiuk A, et al. BLP24 Liposome Vaccine, a MUC1 Vaccine for the Treatment of Non-Small Cell Lung Cancer. Proceedings from the 23rd annual Chemotherapy Foundation Symposium. 2005. New York. Abstract #49.