WHAT'S NEW IN CANCER IMMUNOTHERAPHY 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.
Researchers are also studying other ways of making these drugs safer and more effective. For example, because mAbs are proteins, they can actually make the body’s immune system react against them. This can lead to side effects, as well as destroying the mAbs. Newer forms of mAbs are less likely to cause immune reactions.
Researchers are also looking to see if using only parts of antibodies can make these drugs work better. Another approach under study is to combine parts of two antibodies together (known as a bispecific antibody). One part might attach to a cancer cell, while the other could attach to an immune cell, bringing the two together.
New types of mAbs are now being studied for use against many types of cancer.
Newer cancer vaccines
Vaccines are not yet a major type of treatment for cancer. Researchers have been trying to develop vaccines to fight cancer for decades, but this has proven to be harder than was first thought. As researchers have learned more over the years, the immune system is very complex. It has also become clear that cancer cells have different ways of eluding the immune system, which makes creating effective vaccines difficult.
But researchers are using the knowledge gained in recent years to improve how they develop cancer vaccines. For example, vaccines are now often given along with other substances (called adjuvants) that help boost the body’s immune response, which might help the vaccines work better.
Researchers are also studying the best way to give vaccines, looking to see if they work better when used alone or with other types of cancer treatments.
TYPES OF CANCER VACCINES
Many different types of vaccines are now being studied to treat a variety of cancers.
Tumor cell vaccines: These vaccines are made from actual cancer cells that have been removed from the patient during surgery. The cells are altered in the lab to make them more likely to be attacked by the patient’s immune system and then injected back into the patient. Their immune system then attacks these cells and any similar cells still in the body.
Most tumor cell vaccines are autologous, meaning the vaccine is made from killed tumor cells taken from the same person in whom they will later be used. Other vaccines are allogeneic, meaning the cells for the vaccine come from someone other than the patient being treated. Allogeneic vaccines are easier to make than autologous vaccines, but it’s not yet clear if one type works better than the other.
Antigen vaccines: These vaccines boost the immune system by using only one antigen (or a few), rather than whole tumor cells. The antigens are usually proteins or pieces of proteins called peptides.
Antigen vaccines can be specific for a certain type of cancer, but they are not made for a specific patient like autologous tumor cell vaccines are.
Dendritic cell vaccines: These vaccines have shown the most success so far in treating cancer. Sipuleucel-T (Provenge), which is used to treat advanced prostate cancer, is an example of a dendritic cell vaccine.
Dendritic cells are special immune cells in the body that help the immune system recognize cancer cells. They break down cancer cells into smaller pieces (including antigens), then hold out these antigens so other immune cells called T cells can see them. The T cells then start an immune reaction against any cells in the body that contain these antigens.
Dendritic cell vaccines are autologous vaccines (made from the person in whom they will be used), and must be made individually for each patient. The process used to create them is complex and expensive. Doctors remove some immune cells from the patient’s blood and expose them in the lab to cancer cells or cancer antigens, as well as to other chemicals that turn the immune cells into dendritic cells and help them grow. The dendritic cells are then injected back into the patient, where they should provoke an immune response to cancer cells in the body.
Vector-based vaccines: These vaccines use special delivery systems (called vectors) to make them more effective. They aren’t really a separate category of vaccine; for example, there are vector-based antigen vaccines.
Vectors are special viruses, bacteria, yeast cells, or other structures that can be used to get antigens into the body. The vectors are often germs that have been altered to make sure they can no longer cause disease.
Vectors can be helpful in making vaccines for a number of reasons. First, they can be used to deliver more than one cancer antigen at a time, which might make the body’s immune system more likely to mount a response. Second, vectors such as viruses and bacteria might trigger their own immune responses from the body, which could help make the overall immune response even stronger. Finally, these vaccines might be easier and less expensive to make than some other vaccines.
Some common cancers in which vaccines are being tested
Some of the more common types of cancer in which vaccines are now being studied include:
Brain tumors (especially glioblastoma)
Drugs that target immune system checkpoints
As mentioned in the section “Non-specific cancer immunotherapies and adjuvants,” the immune system has checkpoints to keep itself from attacking other normal cells in the body. Cancer cells sometimes take advantage of these checkpoints to avoid being attacked by the immune system.
CTLA-4: The CTLA-4 checkpoint molecule, which is found on T cells, can be blocked with drugs such as ipilimumab(Yervoy). This leads to a general boost in the immune system, which helps it attack cancer cells. But this drug can also allow the immune system to attack some normal cells in the body, which can lead to serious side effects in some people.
PD-1/PD-L1: Another important checkpoint molecule is the PD-1 protein found on T cells, especially those in tumors and the nearby environment. Cancer cells sometimes have large amounts of the corresponding PD-L1 protein on them, which lets them escape immune system attack.
Drugs that target PD-1 or PD-L1 boost the immune system, but they seem to do so in a more specific way than ipilimumab.
In early clinical trials, the anti-PD-1drug nivolumab has been shown to help shrink some melanomas, kidney cancers, and non-small cell lung cancers. Many of these tumor responses have been long-lasting so far, and the side effects have generally not been as serious as with ipilimumab. Larger clinical trials are now studying this drug, both alone and combined with other treatments.
Pembrolizumab (formerly lambrolizumab) is another drug that targets PD-1. It has shown good early results against melanoma, and it is now being tested against other types of cancer as well.
Many other drugs that target either PD-1 or PD-L1 are now being tested in clinical trials as well, both alone and combined with other drugs.
Other ways to boost the immune system
Some other forms of immunotherapy are being studied to try to boost specific parts of the immune system. These types of treatments show promise, but they are complex and so far are available only through clinical trials being done at major medical centers.
Chimeric antigen receptor (CAR) T-cell therapy
This is a promising new way to get immune cells called T cells to fight cancer. For this technique, T cells are removed from the patient’s blood and genetically altered in the lab to have specific antigen receptors (called chimeric antigen receptors, or CARs) on their surface. These receptors will attach to proteins on the surface of cancer cells. The T cells are then multiplied in the lab and infused back into the patient’s blood, where they can now seek out the cancer cells and launch a precise immune attack against them.
This technique has shown very encouraging results in early clinical trials against some advanced, hard-to-treat types of leukemias and lymphomas. In many people the cancer could no longer be detected after treatment, although it’s not yet clear if these people have been cured.
Some people have had serious side effects from this treatment, including very high fevers and dangerously low blood pressure in the days after it’s given. Doctors are learning how to manage these side effects.
Doctors are still improving how they make the T cells and are learning the best ways to use them. They are also studying whether this treatment will work for other types of cancer. CAR T-cell therapy is only available in clinical trials at this time.
Tumor-infiltrating lymphocytes and interleukin-2 (IL-2)
Researchers have found immune system cells deep inside some tumors and have named these cells tumor-infiltrating lymphocytes (TILs). These T 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 cancer, 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 might not be able to get TILs from all patients.