Delving Into Immunotherapy to Treat Cancer

February 19, 2019

Understanding how the immune system controls itself has led to impressive cancer treatment gains.

Immunotherapy is a rapidly evolving strategy that enlists the body’s own immune system to fight cancer. These treatments work by stimulating the production and activity of T cells, which exist naturally in the body and have the ability to recognize and kill cancer cells.

Types of cancer that can be treated with FDA-approved forms of immunotherapy include melanoma, multiple myeloma, Hodgkin lymphoma, acute lymphoblastic leukemia and kidney, bladder, lung, prostate and head and neck cancers. Immunotherapies are also being tested in other forms of cancer, including breast, head and neck, liver, pancreatic, colorectal and blood cancers. Combinations of these kinds of drugs with each other, or with other types of anti-cancer therapies, are also emerging as potentially more effective for some patients.

While immunotherapies don’t cause the hair loss that comes with chemotherapy, they can spark nausea, rash, fever, chills, fatigue, diarrhea or even severe autoimmune reactions. These drugs can also be very expensive.

Cytokines

Immune Checkpoint Inhibitors

That’s a No-No

SOME PATIENTS WITH CANCER are considered poor candidates for immunotherapy.

Despite all the fanfare about immunotherapies in cancer care, these drugs are not for everyone. Those with certain other conditions are not good candidates for the drugs, and should mention these concerns to their oncologists. Here are three potential contraindications to immunotherapy use, according to Marianne Davies, an oncology nurse practitioner at the Smilow Cancer Hospital at Yale-New Haven and an assistant professor at the Yale School of Nursing:

  • Autoimmune Conditions. Because immunotherapy works by activating T cells to attack cancer, it can also inflame healthy tissues, meaning that patients with autoimmune conditions, such as lupus, rheumatoid arthritis or Crohn’s disease, who already have hyperactive immune systems, are not appropriate for the therapy. “It has the potential to have a significant increase in morbidity, perhaps even mortality, for those patients,” cautions Davies. Similarly, patients who have undergone a prior organ transplant or who have a history of liver damage would not be good candidates for the therapy.
  • Steroid Use. Ongoing use of steroids to treat a health condition other than cancer is also contraindicated, since steroids may suppress the effects of immunotherapy. As a result, unless such patients can be tapered off the steroids, they are not considered good candidates for immunotherapy. It’s true that steroids are sometimes transiently used in patients who have been taking immunotherapy, to treat immune-related side effects. However, immunotherapy is often temporarily or permanently halted during the course of this steroid treatment. In addition to steroids, patients should be monitored for all prescription and nonprescription medications, including vitamins and herbal supplements, to make sure those products are safe to take along with immunotherapy, and will not diminish the immunotherapy’s effectiveness.
  • Aggressive Disease. Patients with a very high tumor burden or rapidly growing cancers may want to opt for chemotherapy or radiation — or, in the case of brain lesions, stereotactic radiosurgery — before moving on to immunotherapy, because these treatments work more quickly than immunotherapy.

So far, only 20 to 30 percent of patients with cancer respond to immunotherapies, and researchers are working to find out why, and how to make the most of the treatments. Some response can be very long-lasting, and even curative, so there is much interest in refining this approach and expanding the number of patients and types of tumors that can be successfully treated.Some cytokines, such as interleukins and interferons, which are found naturally in the body, can also be produced in the laboratory and given to patients to change the way their immune systems are regulated, potentially stimulating immune responses. These approved drugs are used to treat melanoma, kidney and bladder cancers, although they work only in a minority of those patients, and side effects can be severe.While T cells have cancer-killing ability, they are normally held somewhat at bay by “inhibitory checkpoints” in the immune system. The job of these checkpoints is to keep the T cells from engaging in out-of-control activity. The problem with this system is that cancers can hide in the body by sending out the same signals as these checkpoints, along the cell-signaling pathways PD-1/PD-L1 or CTLA-4; this way, T cells don’t recognize or fight them.

One group of immunotherapy drugs blocks this kind of signaling so that the checkpoints no longer have a hold over the activity of T cells. This frees up the T cells to fight cancer. However, in doing so, the immune cells also attack some normal tissue, causing a variety of side effects.

Monoclonal Antibodies

So far, checkpoint inhibitors have been approved for the treatment of advanced melanoma, metastatic non-small cell lung cancer and renal cell carcinoma. Such drugs are being tested in clinical trials for the treatment of breast and bladder cancer and Hodgkin lymphoma, among others.When the immune system is provoked by foreign cells and other substances, it reacts by activating T cell lymphocytes (a type of white blood cell), which can directly kill foreign cells, and by stimulating B cell lymphocytes to make proteins called antibodies. These antibodies are drawn to other proteins known as antigens, which sit perched on the outsides of cells; drawn like magnets, the antibodies attach to the antigens. Once in place, the antibodies call in the immune system to destroy the cells to which they are attached.

Adoptive T Cell Therapy

Chimeric Antigen Receptor Therapy

Vaccines

Monoclonal antibodies, which are designed to seek and destroy specific cancer-associated antigens, can be made in a lab and then given to patients. Some of these strictly target one type of antigen, but cannot always fight tumors on their own. Bispecific antibodies may be more effective, because they can bind to, and destroy, two different antigens present on one or many cells. One antibody enlists a T cell while the other targets a tumor, bringing the main partners of the immune process together.If a good immune response is already happening in a patient’s body, adoptive T cell therapy may improve it. In adoptive cell transfer, a sample of a patient’s tumor is sent to a lab, where T cells inside the tumor are removed and stimulated to increase in number. Then, this larger group of T cells, known as tumor infiltrating lymphocytes (TILs), is returned to the patient intravenously. This experimental method has been shown to induce complete, durable regression of certain malignancies, including a number of blood cancers and melanoma.Like adoptive T cell therapy, chimeric antigen receptor (CAR) therapy involves manipulating a patient’s T cells in a lab. But in this case, the T cells are genetically modified to express a specific protein, which prepares them to hone in on, and attack, specific proteins on a particular kind of cancer cell. When the CAR T cells are infused into the patient’s body, they can multiply and continue to eradicate tumors over time. Clinical trials have shown that this method can have significant anti-tumor activity in acute leukemia, neuroblastoma, chronic lymphocytic leukemia and B cell lymphoma. This method is still experimental, and trials of CAR T cell therapy targeting a variety of other adult and pediatric malignancies are in progress.A host of vaccines, some approved and some experimental, also fall into the immunotherapy category. There are four main basic types:

  • Vaccines that use an engineered inactivated virus to deliver an agent such as a cytokine that can cause the destruction of cancer cells.
  • Vaccines that send whole tumor cells into the body with the goal of drawing the immune system’s attention to the foreign cells so it will fight them — as well as the tumor cells already growing in the body.
  • Infused dendritic cell vaccines, which are made uniquely for each patient using his or her own white blood cells, mixed with an agent that will help the body mount an immune response against cancer cells.
  • Peptide vaccines. These include a small peptide (amino acid) sequence taken from a tumor-associated antigen. This is mixed with an agent that stimulates dendritic cells to process the peptide sequence; in turn, that causes the immune system to recognize and fight any antigens that contain the sequence.

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