The FDA has approved several cancer immunotherapies, including Bacille Calmette-Guérin (BCG), interferon-alfa (IFN-alfa), interleukin-2 (IL-2), and the monoclonal antibodies listed above.

Many other immunotherapies have shown promising results and are moving through the testing process in clinical trials. The cancers listed here are being studied most intensively, but treatments for other cancers are also being looked at.

Melanoma

Melanoma is probably the most-studied cancer when it comes to immunotherapy. Part of this is because doctors think this cancer may be more vulnerable to immune system responses. In rare cases, these cancers have been seen to shrink or even disappear without treatment. It is thought that this may be because of an effective immune response by the body.

Another reason immunotherapy has been studied more in melanoma is because other treatments, like chemotherapy, aren't very effective against this cancer.

• The cytokines IFN-alfa and IL-2 are approved to treat people with metastatic melanoma.

• The non-specific immune stimulant BCG has not been shown to prolong life or delay relapse when used alone, but it is being tested along with melanoma vaccines and other immunotherapies.

• Although no melanoma vaccines are FDA approved yet, recent studies have found that some autologous and allogeneic tumor cell vaccines, as well as antigen vaccines, have shrunk tumors and helped some patients live longer. Dendritic cell vaccines have also been shown to shrink tumors in some patients.

• A recent small study showed that treating patients with tumor-infiltrating lymphocytes (TILs), immune system cells found in tumors, could shrink melanoma tumors and possibly prolong life too. Another study found that T cells from the blood that had their genes altered in the lab could cause tumors to shrink in a small fraction of patients.

• Very early study results have suggested that suppressing regulatory T cells with denileukin diftitox (Ontak) can allow the immune system to fight cancers better, making some tumors shrink.

• Clinical trials are continuing for these and other melanoma immunotherapies.

Kidney cancer

Immunotherapy has been studied a great deal for advanced kidney cancer, least in part because other treatments like chemotherapy often aren't helpful.

• Two cytokines, IL-2 and IFN-alfa, are treatment options for people with advanced kidney cancer.

• Whole tumor cell vaccines given along with the adjuvant BCG have shrunk tumors in a small number of people with advanced kidney cancer.

• Researchers are studying DNA vaccines that insert genes (segments of DNA) into cancer cells, causing the cells to make cytokines. These cytokines help the immune system recognize the cancer cells and also help activate immune system cells to attack those cells.

• Tumor-infiltrating lymphocytes (TILs) are also being studied to fight kidney cancer. They can be removed from the body and stimulated in the lab by cytokines. When put back into the body, they become more effective than immune cells from the bloodstream.

• Some studies have suggested that bevacizumab (Avastin), a monoclonal antibody that slows blood vessel growth in tumors, may be effective against kidney cancer. This is being studied further.

Leukemias, lymphomas, and myelomas

Several immunotherapies are now used to treat these blood cell cancers, and many more are being studied.

• Interferon-alfa is often used to treat people with hairy cell leukemia, chronic myelogenous leukemia, follicular lymphoma, multiple myeloma, and cutaneous (skin) T cell lymphoma. In some cases, interferon is used along with chemotherapy.

• Denileukin diftitox (Ontak), a combination of IL-2 and diphtheria toxin, is sometimes used to treat cutaneous T cell lymphoma.

• Rituximab (Rituxan), a monoclonal antibody (MAb), is used to treat some kinds of B cell non-Hodgkin lymphoma. Clinical trials are currently testing rituximab against other lymphomas, leukemias, multiple myeloma, and other diseases.

• Ibritumomab tiuxetan (Zevalin) and tositumomab (Bexxar) are radiolabeled monoclonal antibodies used to treat non-Hodgkin lymphoma, usually in people who aren't helped by other treatments such as chemotherapy or rituximab. They are now being tested to see if they might be helpful earlier in the course of this disease.

• Several other MAbs are being studied in clinical trials for people with leukemia, lymphoma, and multiple myeloma. Anti-idiotype vaccines have shown promising results in clinical trials against B-cell non-Hodgkin lymphomas, but are not yet FDA approved.

Breast cancer

In terms of immunotherapy, only monoclonal antibodies (MAbs) have been approved for use against breast cancer so far. But many other forms of treatment are being studied.

• The MAb trastuzumab (Herceptin) is used in women with breast cancer whose cancer cells have too many copies of the HER2/neu gene. These genes make extra receptors for growth-stimulating factors on the cells, which results in a more aggressive form of breast cancer. Trastuzumab attaches to the receptors, blocking the access of the growth factors to the cancer cells and slowing their growth. Other HER2/neu antibodies are now being studied in clinical trials.

• Bevacizumab (Avastin), a monoclonal antibody that slows blood vessel growth in tumors, is being studied along with chemotherapy in some women with advanced breast cancer.

• Some interferons and interleukins have shown promise against breast cancer, particularly when used along with tumor vaccines or immunotoxins.

• Autologous vaccine therapy has lengthened remission and survival times of some women with early breast cancer. This approach is being studied further.

• A HER2/neu peptide (a small part of the protein made by the HER2/neu gene), used as the antigen in a vaccine, has been shown to cause an increased immune response against the HER2/neu receptor on cancer cells; it is under study.

• Other specific antigen vaccines are also promising. These vaccines are almost always used after primary therapy (lumpectomy and radiation therapy, or mastectomy) and sometimes together with hormonal therapy or chemotherapy, to try to keep the cancer from coming back.

Prostate cancer

Immunotherapy is not routinely used in treating prostate cancer. Most prostate cancer immunotherapies now being studied are vaccines. They are designed to cause immune responses to antigens present only on prostate cells, such as prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA).

• In one approach that has shown promise, researchers take dendritic cells from a patient's bloodstream and treat them in the lab with prostate cancer antigens. When put back in to the patient, the dendritic cells can show these antigens to other immune system cells, which are then better able to recognize and attack the cancer cells. One fairly small study showed that this approach may help men with advanced prostate cancer live longer.

• GVAX is an autologous whole cell vaccine. It is made by removing cancer cells from the patient during surgery and modifying them in the lab to express GM-CSF (to help stimulate the immune system). The cells are irradiated so they can't grow any more. They are then injected back into the patient to cause an immune response. Early studies of patients with advanced prostate cancer that no longer responded to hormone therapy have shown some promising results in terms of survival time. This vaccine is now being tested against the current standard chemotherapy regimen for prostate cancer.

• Researchers also are looking into using a part of the prostate-specific antigen (called a peptide) as the basis of a vaccine.

• DNA vaccines, monoclonal antibodies, and cytokines have also shown promise and are being tested in clinical trials.

Colorectal cancer

Several monoclonal antibodies are now used to treat colorectal cancer. Clinical trials are also being done using vaccines and many other immunotherapies as adjuvants to surgery, with and without chemotherapy.

• Bevacizumab (Avastin) is a monoclonal antibody against vascular endothelial growth factor (VEGF). By attacking VEGF, the antibody stops tumors from being able to form new blood vessels. It is used along with chemotherapy against advanced colorectal cancer.

• Cetuximab (Erbitux) is a monoclonal antibody that attacks the epidermal growth factor receptor (EGFR), which normally signals cancer cells to grow and divide. It is used against advanced colorectal cancer, usually along with chemotherapy, in people whose cancer is no longer responding to other treatments.

• Another monoclonal antibody, panitumumab (Vectibix), also targets EGFR. Unlike cetuximab, this MAb has no parts that come from a mouse, so it may be less likely to cause an allergic reaction when it is given. Panitumumab is used to treat advanced colorectal cancer.

• A number of autologous and allogeneic tumor cell vaccines have shown early promise, but so far none have improved patient survival time.

• Some carcinoembryonic antigen (CEA) vaccines have caused an improved immune response (measured by blood tests) in a large percentage of colorectal cancer patients, but the studies have not been going on long enough to see whether this improves remission or survival times.

Cervical cancer

Infection with the human papilloma virus (HPV) plays an important role in causing cervical cancer. HPV vaccines are now approved for use to help prevent cervical cancer. Other vaccines that may help treat this cancer are now being tested in clinical trials.

• Some HPV vaccines are like more traditional vaccines against infections. They are intended to make women immune to HPV, so that when they are exposed to these viruses they will not develop infections. By avoiding persistent HPV infection, most cervical cancers may be prevented. One of these vaccines (Gardasil) is highly effective in protecting against infections from the 2 types of HPV that cause 70% of cervical cancers. This vaccine is now approved for use in females aged 9 to 26. But it is still new. Although it has been shown to help prevent pre-cancerous lesions, it's not yet clear how well it will protect against cervical cancer. This and other preventive vaccines are being studied further.

• Other vaccines are meant to help women who already have advanced cervical cancer. These vaccines attempt to cause an immune reaction to the parts of the virus that contribute to the growth of cervical cancer cells. This may kill the cancer cells or stop them from growing.

• Interferons and interleukins are also being studied in women with metastatic cervical cancer.

Ovarian cancer

Immunotherapy is not used routinely to treat ovarian cancer. Several types of immunotherapy, including cancer vaccines and MAbs, are now being studied.

• Injection of interleukin-2 (IL-2) directly into the peritoneal cavity (the body cavity that contains the ovaries, uterus, and digestive organs) of women with recurrent ovarian cancer is currently being studied. Early studies suggest the treatment may increase the length of remissions after surgery.

• Placing tumor-infiltrating lymphocytes (TILs) along with interleukin-2 directly into the peritoneal cavity has also shown promise and is being studied.

• Trastuzumab (Herceptin), a monoclonal antibody, is being studied to see if it may help the roughly 20% of women with ovarian cancer whose cells have too many copies of the HER2/neu gene.

• A monoclonal antibody that attaches to certain antigens on ovarian cancer cells and to specific spots on T cells (a bispecific antibody) has shown promise when used with IL-2. The antibody causes T cells to bind to and attack the cancer cells.

• Early studies have shown that radiolabeled MAbs against ovarian cancer may help more women live longer.

• Several forms of antigen vaccines are being studied to treat ovarian cancer.

Lung cancer

Better treatments are needed for lung cancer,, especially for advanced disease. Immunotherapy may help people live longer without the severe side effects sometimes seen with chemotherapy. Thus far, only monoclonal antibodies have been approved for use against lung cancer, although many other forms of immunotherapy are being studied.

• The monoclonal antibody bevacizumab (Avastin) slows the growth of tumor blood vessels by targeting the VEGF protein. For patients with non-small cell lung cancer (NSCLC), it can be added to standard chemotherapy and it may help them live longer than chemotherapy alone.

• GVAX is an autologous whole cell vaccine. It is made by removing cancer cells from the patient during surgery and modifying them in the lab to express GM-CSF (to help stimulate the immune system). The cells are irradiated so they can't multiply. They are then injected back into the patient to cause an immune response. Early studies of patients with advanced NSCLC have shown some responses to this vaccine, but further studies are needed.

• BLP25 is a peptide (antigen) vaccine that is encased in a fat droplet (liposome) to make it more effective. A small study of patients with advanced NSCLC suggested it may improve survival time. Larger studies are needed to confirm this.

Revised: 03/18/2008