The term immunotherapy refers to a branch of medicine that investigates methods of bolstering the body’s natural immune defense to combat various diseases. Gaining a great deal of momentum recently is the field of immuno-oncology, which applies the advances in immunotherapy to the treatment of cancers.
A person’s immune system consists of a number of different specialized cells and other biological products that respond to infections, and these natural defenses can also help protect people from cancer. What makes the field of oncology especially trying is cancer’s tendency to mutate at a fast rate, which allows it to evolve mechanisms to escape the body’s immune response. Often, cancer cells trick the body’s immune system into believing that they are normal, healthy cells. Another mechanism involves the use of proteins that prevent attacks from the immune system’s T cells.
Immuno-oncology is not a new idea. In fact, scientists have been developing immunotherapy strategies to combat cancers for decades, but these approaches have had mixed success. However, in recent years, researchers have made a number of notable strides that have renewed excitement about this approach to cancer treatment. Many medical research centers have launched programs to explore the potential of these treatments through translational work and clinical trials.
The following is a look at some of the immuno-oncology strategies that are generating the most excitement:
Checkpoint Blockers and Monoclonal Antibodies
Cancer cells have evolved to generate proteins found in the body that disable T cells from attacking and killing them. Researchers at leading facilities like the Dana-Farber Cancer Institute have investigated the development of monoclonal antibody drugs that would stop these cells from inhibiting the T-cell attack. Dana-Farber researchers identified that “checkpoint blocker” molecules like PD-1, PD-L1, and CTLA-4 are able to circumvent the cancer cell’s defense system so that T cells can identify and destroy the cancer. Monoclonal antibodies that attach to and therefore inhibit cancer antigens are also being developed. These antigens play a key role in cancer growth and development,. Some monoclonal antibodies can also carry radioactive substances, toxins, and other drugs to cancer cells recognized by the antibody. This system provides a way of delivering drugs directly to cancer cells.
Clinical trials for these monoclonal antibodies, given in combination or alone, were first conducted in patients with advanced melanoma. Some patients showed remarkable improvement with these treatments. In certain cases, patients’ lives were extended up to a decade. With such promising results, clinical trials have been launched to explore the treatment’s effectiveness with other diagnoses, including cancers in the liver, lungs, breasts, head, and neck. While reports are early, results have shown additional benefits in these cancers.
One of the major drawbacks of these therapies is that not all patients respond to them. In fact, only a minority of patients show improvement. Once the reason for this is known, therapies can be made effective for a wider population. Other issues include side effects, which can compound when several therapies are given in combination. At the same time, researchers believe that monoclonal antibodies may emerge as a backbone of treatment that is as important as chemotherapy. In certain cancers, immunotherapy may eventually replace chemotherapy.
Another promising field under the umbrella of immuno-oncology is cancer vaccination, which could play a role in both preventing and treating various cancers. These vaccinations do not necessarily target cancer directly, but instead fight diseases that are precursors to cancer. For example, a vaccine to prevent human papilloma virus (HPV) has been developed, which could dramatically decrease the rate of cervical cancer. HPV can also lead to cancers of the mouth and throat.
Other vaccines are being investigated to help train the body’s natural immune defenses to identify and attack cancer cells. In 2010, Provenge, the first cancer vaccine, was approved for use in humans. This vaccine triggers an immune response against prostate cancer, but it must be customized to the biology of each individual patient.
CAR T Cells
The acronym CAR stands for “chimeric antigen receptor.” CAR T cell treatment is still highly experimental, but the success of earlier trials, especially in cancers that are traditionally difficult to treat, has made patient demand for this treatment rise sharply.
During treatment, CAR T cells are extracted from the patient’s own blood and then trained in a laboratory setting to recognize and attack tumor cells. After this training period, the cells are returned to the patient’s blood system, where they function as high-efficiency cancer fighters. CAR T cell treatments have shown a great deal of success in particularly difficult-to-treat forms of leukemia. They are being tested for use in other blood cancers, as well as solid tumors, including brain cancers and glioblastoma, which is a cancer that affects the central nervous system.