Traditional approaches to cancer treatment involve surgery, which is the manual removal of abnormal cells during early stages; chemotherapy, which aims to poison the abnormal cells; and irradiation, which “burns” the cells. Unfortunately, these methods are not very targeted, meaning that they also do damage to healthy cells. Older patients or those with complicating diagnoses may not be good candidates for any of these options, especially due to the immunosuppression that results from both radiation and chemotherapy. Furthermore, there is no guarantee of eradicating all abnormal cells.
Because of the shortcomings of traditional treatment options, researchers are exploring immuno-oncology as a new way of combatting cancer. Immunotherapy involves improving the body’s own immune response to cancer—a natural way to combat disease that is less toxic to healthy cells than other approaches. This treatment has shown promise when used alone or in combination with other therapies.
At present, researchers are pursuing the following three main branches of immunotherapy:
Cell-Based Approaches to Immuno-Oncology
The cell-based approach to cancer immunotherapy involves injecting activated immune cells directly into a patient’s bloodstream. This approach has a two-fold effect. First, the injection provides immune cells that can directly combat cancer cells. Second, the cells activate other parts of the immune system to attack the cancer.
Cell-based immuno-oncology typically involves dendritic cells, which act as a bridge between innate and adaptive immunity. Dendritic cells can induce an immune response when activated by an antigen by triggering T-cells. A common approach to experimental treatment is to extract dendritic cells from the patient’s body and then expose them to tumor peptides and adjuvants that drive the creation of new immune cells in the body. The transformed cells form a sort of vaccine to boost the immune system.
Researchers have also been able to produce a cell-based response in situ by inducing the production of GM-CSF in tumor cells to help the immune system better distinguish between self and non-self molecules. This process is aided by Interleukin 2, which regulates white blood cell activity. These methods can trigger cytotoxic T-cells to eliminate cancer cells.
To make the attack long lasting, some researchers have used antibodies that are specific to the receptors found on the surface of dendritic cells. Then, proteins present on tumor cells can be added to antibody-coated receptors so that the immune system learns to attack cells with these antigens.
Another approach involves the use of vectors, which are artificially cultured pieces of viral DNA containing directions to express GM-CSF or other adjuvants. The virus has no negative effect on the body, but it expresses antigens that can combine naturally with dendritic cells.
Antibody-Based Cancer Immunotherapy
Researchers typically use mouse models to create monoclonal antibodies in the laboratory, but these antibodies carry the risk of immune rejection, which can lead to harmful side effects. To combat this possibility, immuno-oncology researchers often use chimeric antibodies that combine both mouse and human antibodies. Researchers may also use human antibodies derived from humans with parallel amino acid sequences. Regardless of the host used, the production process involves introducing antibody-producing plasma cells with cancer-specific antigens. Later, a cancerous immune cell is also added, and the combination is screened for antibody production.
When researchers isolate antibodies, they test them for their ability to bind to the desired antigen. Then, they clone the most effective option, which is what gives rise to the term “monoclonal.” The resulting monoclonal antibody is specific to one type of antigenic protein, which allows it to target only specific cancer cells.
Once generated, monoclonal antibodies have a variety of paths to attack tumor cells. Through antibody-dependent, cell-mediated cytotoxicity, the antibody binds to the surface of the tumor cells and then releases enzymes that trigger programmed cell death. Antibodies may also trigger the complement system when they bind. Then, components of the complement pathway engulf the tumor cell and perforate its membrane to cause the destruction of cells. Antibodies can also destroy target cells through cell signaling. In this strategy, the antibodies block important binding sites that prevent the cancer cell from making connections that are necessary for life. As a result, the cancer cells undergo apoptosis, or programmed cell death.
Immuno-Oncology through Cytokines
Cytokines regulate immune signals. Researchers have looked into cytokines as a means of triggering cell death in tumors. The most commonly used cytokines include interferons and interleukins. Interferons act against viral infections, but they have also proven useful in the treatment of certain cancers, such as hairy-cell leukemia, chronic myeloid leukemia, follicular lymphoma, and Kaposi’s sarcoma. Interleukins are also known as a “T-cell growth factor” because they promote the health and proliferation of these T-cells and other immune system cells. As a result, the entire immune system is boosted. The therapy has been tested in malignant melanoma and renal cell carcinoma. Of course, like all signaling pathways, there is a delicate balance between boosting the immune system and causing other adverse events.