Immunotherapy is when parts of a sick person’s immune system are used to combat disease and infection, in this case cancer. This is done by stimulating the immune system to work harder, or giving the immune system components to combat the disease or infection.
Doctor William Coley discovered that post-surgery infection seemed to help some cancer patients. He later attempted to treat cancer patients by infecting them with bacteria. This is the basis for modern immunotherapy, although now we do not infect patients; we activate their immune systems using various methods or give their immune systems tools to fight with.
Some types of cancer immunotherapy boost the immune system as a whole, while others use the immune system to attack cancer cells directly. Researchers have managed to find a way to get a person’s immune system to recognize cancer cells in the body and to strengthen its response.
There are three types of cancer immunotherapy: monoclonal antibodies, cancer vaccines, and non-specific immunotherapy’s. The trick with cancer immunotherapy is figuring out which antigens are on the cancer cell, or which antigens are involved with the cancer or immune system.
Types of Immunotherapy and Their Cancer Applications
Monoclonal antibodies are man-made or engineered from a patient’s white blood cells, and are used for targeting the immune system or specific antibodies on the cancer cells.
The first step in making monoclonal antibodies is to identify the right antigen to target. This is difficult with cancer since there are many antigens involved. Some cancers are more resilient to monoclonal antibodies then others but, as more antigens are linked to certain types of cancers, the monoclonal antibodies become more effective.
There are two types of monoclonal antibodies; the first is conjugated monoclonal antibodies. These have radioactive particles or chemotherapy drugs attached to the antibody. The antibody searches for and attaches to the cancer cell where the drug or particle can be administered directly. This therapy is less harmful then more traditional means of chemo or radioactive therapy.
The second type is naked monoclonal antibodies and, as the name suggests, these do not have any chemotherapy drug or radioactive material attached to them. This type of antibody works on its own, though they still attach to the antigens on cancer cells as well as other non-cancerous cells or free floating proteins.
Some boost immune response by acting as a marker for T-cells when attached to cancer cells. Others boost the immune system as a whole by targeting immune system checkpoints. An example of naked monoclonal antibodies (NmAbs) is the drug “Alemtuzumab” made by Campath. Alemtuzumab is used for patients with chronic lymphocytic leukemia (CLL). The antibodies target the CD52 antigen on lymphocytes, including the leukemia cells, and attract the patients’ immune cells to destroy the cancer cells.
Cancer vaccines, another form of monoclonal antibody, target the immune response towards viruses and infections that can lead to cancer. Using the same principles of a normal vaccine, the primary focus of cancer vaccines is to act as a preventative measure more than a therapeutic measure.Cancer vaccines do not attack the cancer cells directly.
Cancer vaccines work the same as typical vaccines in the way that they stimulate the immune system, however with the cancer vaccine the immune system is targeted toward attacking cancer cells that are created by a virus rather than the virus itself.
It is known that some strains of the human papilloma virus (HPV) are linked to cervical, anal, throat, and some other cancers. Additionally, people with chronic hepatitis B (HBV) have a higher risk of getting liver cancer.
Sometimes, to create a cancer vaccine for HPV, for example, a patient who is infected with the human papilloma virus will have a sample of their white blood cells removed. These cells will be exposed to specific substances that, when reintroduced to the patient’s immune system, will create an increased immune response. The vaccine created in this way will be specific to the person the white blood cells are taken from. This is because the white blood cells will be coded with the person’s DNA allowing the vaccine to be fully integrated into their immune system.
Non-specific cancer immunotherapy’s do not target cancer cells directly but stimulate the entire immune system. This type of immunotherapy generally is done through cytokines and drugs that target immune system checkpoints.
The immune system uses checkpoints to keep itself from attacking normal or self-cells in the body. It uses molecules or immune cells which are activated or inactivated to start an immune response. Cancer cells can go unnoticed by the immune system because they can have certain antigens that mimic those of the body’s self-cells so the immune system does not attack them.
Cytokines are chemicals that some immune system cells can create. They control the growth and activity of other immune system cells. There are two types of cytokines: interleukins and interferon’s.
Interleukins act as a chemical signal between white blood cells. Interleukin-2 (IL-2) helps the immune system cells grow and divide more quickly, by adding more or stimulating IL-2 cells it can increase immune response and success rate against certain cancers.
Interferon’s help the body resist viruses, infections, and cancers. They do this by boosting the ability of certain immune cells to attack cancer cells and may slow the growth of the cancer cells. The use of interferon’s has been approved for cancers such as hairy cell leukemia, chronic myeologenous leukemia (CML), types of lymphoma, kidney cancer, and melanoma.
What’s New in Cancer Immunotherapy Research?
Immunotherapy itself isn’t a new field, even with its application towards the treatment of cancer. But as more research is done toward what causes cancer and how to better detect it, we are better able to come up with a defense against the disease and fight back.
Many pharmaceutical companies are coming up with drugs to combat cancer. Though not much is said about the drugs while in the planning stage (for security reasons), there are clinical trials for drugs that are proving to be effective in treating cancer. One such drug is CAR T-cell (Chimeric Antigen Receptor) therapy, a monoclonal antibody used for treating acute lymphoblastic leukemia.
This therapy uses t-cells collected from a patient’s blood and genetically engineers them to produce special receptors on the surface, chimeric antigen receptors. The patient is inoculated with the modified white blood cells, which then seek out and kill cancer cells with a specific antigen.
Dr. SA Rosenberg told Nature Reviews Clinical Oncology that CAR T-cell therapy can” become a standard therapy for some B-cell malignancies”. The Children’s Hospital of Philadelphia conducted trials for leukemia and lymphoma using CAR T-cell therapy. All signs of cancer disappeared from 27 out of 30 patients, 19 of those 27 remained in remission, 15 people are no longer receiving therapy, and 4 of the people are moving on to receive other forms of therapy.
This marks a very successful treatment, and with such a high rate of remission you can look forward to seeing more CAR T-cell treatments (and others like it) in the future. CAR T-cell therapy is “much more potent than anything we can achieve [with other forms of immunotherapy being considered]” says Dr. Crystal Mackall from the National Cancer Institute (NCI).
Dr. Lee from NCI says that the “findings strongly suggest that CAR T-cell therapy is a useful bridge to bone marrow transplant for patients who are no longer responding to chemotherapy”. With the symptoms of monoclonal antibody therapy being less severe than chemotherapy, it is looking to be a more suitable and less destructive form of therapy.
Lung cancer has a low survival rate of roughly 15% over 5 years compared to breast cancer’s 89%. Nivolumab is a drug used for the treatment of non-small cell lung cancer and melanoma. It was tested on a group of 129 with lung cancer.
Participants were giving dosages of 1, 3, or 10mg/kg of body weight of Nivolumab for up to 96 months. After 2 years of treatment, the survival rate was 25%, a good increase for a deadly cancer like lung cancer. Nivolumab was also tested for people with melanoma, and tests indicated a survival rate increase from 0% over three years without treatment to 40% with the use of Nivolumab.
The drug blocks the PD-1 antigen receptor on white blood cells so cancer cells do not interact with it; this makes iteasier for the immune system to detect the cancer and dispose of it accordingly. During the tests it was discovered that people with the PD-L1 antibody responded to those without, though the reasoning behind it is not yet known.
There is also DNA immunotherapy, which uses the plasmids of an infected person’s cells in order to create a vaccine. When the vaccine is injected into the patient it changes the DNA of certain cells to accomplish a specific task.
The drug SCIB1 by Scancell, currently in phase 2 clinical, is designed for treatment of melanoma. The plasmid in engineered to affect the Tyrosinase-Related Protein 2 (TRP2) antigen in addition with two helper T-cell epitopes. The drug is taken up by dendrite cells and develops an immune response against tumors with TRP2, which inhibits the tumor’s primary and metastatic growth.
A major advantage of SCIB1 is the functioning group will be recognized by the CD64 antigen receptor in dendrite cells. This means an increase in the strength of immune response. Another bonus of SCIB1 is that the drug itself is not very toxic, allowing for higher doses of the drug which means a stronger immune response.
In the future you can expect to see many different types of immunotherapy and for them to combat other infections and diseases besides cancer.