What’s new in immunotherapy research?

Immunotherapy is a very active area of cancer research. Many scientists and doctors around the world are studying new ways to use immunotherapy to treat cancer. Some of these are discussed here.

Newer monoclonal antibodies

Monoclonal antibodies (mAbs) have already become an important part of the treatment for many cancers. As researchers have learned more about what makes cancer cells different from normal cells, they have developed mAbs to exploit these differences. They have also developed newer forms of mAbs, attaching them to drugs or other substances to make them more powerful. New mAbs are now being studied for use against many types of cancer. A few are listed here.

Breast cancer

A conjugated mAb known as trastuzumab-DM1 (or T-DM1) combines the trastuzumab (Herceptin) antibody, which targets the HER2/neu protein, with a chemo drug. It has shown promise in early studies of women whose breast cancer no longer responds to trastuzumab alone.

Another mAb, pertuzumab, targets a different part of the HER2/neu protein. It may be helpful when used along with trastuzumab to treat certain breast cancers.

Leukemias and lymphomas

Several newer mAbs are being studied in clinical trials for people with different types of leukemia and lymphoma.

Ovarian cancer

An mAb that attaches to certain antigens on both ovarian cancer cells and to certain spots on T cells (a bi-specific antibody) has shown promise when used with interleukin-2 (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 some women live longer.

Bevacizumab (Avastin), another mAb, slows the growth of tumor blood vessels by targeting the VEGF protein. It can slow the growth of advanced ovarian cancer, although it's not yet clear if it helps women live longer.

Newer cancer vaccines

Vaccines are not yet considered a major treatment for cancer. But there are many different types of vaccines now being studied to treat a variety of cancers.

Breast cancer

Early studies have found that autologous vaccine therapy may lengthen the 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 HER2/neu protein), 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 being studied further.

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.

Cervical cancer

While HPV vaccines already available may help prevent some of these cancers, other HPV vaccines that may help treat this cancer are now being tested in clinical trials. These vaccines try to cause an immune reaction to the parts of the virus that aid the growth of cervical cancer cells. This may kill the cancer cells or stop them from growing.

Colorectal cancer

A number of autologous and allogeneic tumor cell vaccines have shown early promise in treating colorectal cancer, but so far none have been shown to lengthen survival time.

Some vaccines against the carcinoembryonic antigen (CEA) protein have improved the immune response in a large portion of colorectal cancer patients, but the studies have not been going on long enough to see whether this lengthens remission or survival times.

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 in early studies.

Researchers are also 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.

Lymphoma

Several vaccines have shown promising results in early clinical trials against B-cell non-Hodgkin lymphomas, but they are not yet US Food and Drug Administration (FDA)-approved.

Lung cancer

Stimuvax^® (BLP25) is a peptide vaccine that is encased in a fat droplet (liposome) to make it work better. A small study of patients with advanced non-small cell lung cancer suggested it might improve survival time. Larger studies are being done to try to confirm this.

Melanoma

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. Some newer studies combine vaccines with IL-2 or newer adjuvants to further stimulate the immune reaction. There is a lot of research going on in this area.

Pancreas cancer

GVAX is a tumor cell vaccine. It is made by modifying pancreatic cancer cells 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 into the patient to cause an immune response. In a small early study, patients who got the vaccine combined with the mAb ipilimumab (Yervoy^®), which boosts the immune system, lived longer than expected. This vaccine is now being looked at in larger studies.

Prostate cancer

Many prostate cancer vaccines are designed to cause immune responses to antigens found only on prostate cells, such as prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA).

A version of the GVAX vaccine using prostate cancer cells has shown some promise in early studies. This vaccine is now being tested in larger studies of prostate cancer.

Another prostate cancer vaccine (PROSTVAC-VF) uses a virus that has been genetically modified to contain PSA. The patient's immune system should respond to the virus and begin to recognize and destroy cancer cells containing PSA. Early results with this vaccine have been promising.

Other ways to boost the immune system

Some other forms of immunotherapy now being studied try to boost specific parts of the immune system. These types of treatments have shown promise, but they are complex and so far are available only through clinical trials being done at major medical centers.

Lymphokine-activated killer cell therapy

Scientists can make large numbers of active, cancer-fighting T cells in the lab by treating a small number of a patient's T cells in a test tube with the cytokine interleukin-2 (IL-2). After being returned to a patient's bloodstream, these special cells, now called lymphokine-activated killer cells (or LAK cells), are more effective against cancer cells. Researchers are now testing several ways to use these very active cancer-fighting cells.

LAK cell therapy has shown promising results in animal studies, where it shrunk tumors in animals with lung, liver, and other cancers. Although clinical trials in humans have not yet been as successful, researchers are constantly improving LAK cell techniques. They are testing these newly improved methods against melanoma, brain tumors, and other cancers.

Tumor-infiltrating lymphocyte vaccine with interleukin-2

Researchers have found immune system cells deep inside some tumors and have named these cells tumor-infiltrating lymphocytes (TILs). These cells can be removed from tumor samples taken from patients and made to multiply in the lab by treating them with IL-2. When injected back into the patient, these cells can be active cancer fighters.

Treatments using TILs are being tested in clinical trials in people with melanoma, kidney cancer, ovarian, and other cancers. Early studies of this approach by researchers from the National Cancer Institute have been promising, but its use may be limited because doctors may not be able to get TILs from all patients.