The medical community has made great strides in the last 150 years in treating cancer with procedures like surgery, radiation therapy, chemotherapy, and even vaccines. Immunotherapy represents a cutting-edge new therapeutic tool. Long-term remission, in which cancer disappears for a year or two after treatment, has been achieved in some patients with incurable cancer by reprogramming their immune systems to recognize and kill cancer cells.

Leukemia and metastatic melanoma are just two examples of late-stage cancers that have responded well to immunotherapy, and immunotherapy has only recently been used to treat intermediate-stage lung cancer. The United States Food and Drug Administration (FDA) has approved several types of cancer immunotherapy, and the European Union (EU) is considering doing the same. Some of these medications restore normal function to the immune system by counteracting the suppression caused by cancer, while others reprogramme the patient’s own white blood cells to engage in the fight. In another strategy, antibodies are used to immunize patients against their own tumors, thereby stimulating the immune system to attack the cancer cells. This method is still in the early stages of clinical development.

Unfortunately, immunotherapy is not a viable option or even a success story for all cancer patients. According to an analysis of FDA-approved therapies and US cancer statistics conducted by two medical professionals, 70% of cancer deaths in the US are attributable to cancers for which there are currently no approved immunotherapy treatments. Extreme autoimmune reactions, cancer recurrence, and even death have been reported in patients undergoing immunotherapy.

Different people have different views on whether or not immunotherapy is useful because of the varying results. While it is unclear how immunotherapy will affect cancer treatment in the long run, its development represents a revolutionary shift in the field. Immunotherapy is based on a better understanding of the biochemical mechanisms by which cancer evades the immune system through mutation. Academic immunotherapy research is rapidly being commercialized into individualized and targeted cancer therapies.

The Use of Checkpoint Inhibitors:

T-cells are a type of white blood cell that can recognize and kill invaders; through immunotherapy, these cells can be made to react more strongly to cancer cells. Tumors have the ability to suppress the immune system on their own by producing chemical signals that silence T-cells. Cancer cells also attach to receptors on the surface of T-cells. This sends internal messages that normally keep the immune system from attacking healthy cells.


CAR-T is a novel cancer immunotherapy that enhances T-cells’ homing ability to locate and destroy blood-borne cancer cells. In the United States, CAR-T therapy was initially approved for use on children with aggressive leukemia and later expanded to include use in adults.

Chimeric antigen receptor T-cells (CAR T-cells) are created when a patient’s blood is sent to a lab, where T-cells are isolated and genetically modified to create CARs. These chimeric antigen receptors (CARs) consist of two fused components: an antibody that projects from the surface of a T-cell to recognize a protein on cancerous B-cells (typically CD-19) in the blood, and a receptor inside the T-cell that transmits signals to the cellular machinery. The CAR T-cell attacks the attached cancer cell when the antibody binds to a tumor cell and activates the internal receptor.

In clinical trials, some patients with aggressive leukemia who received CAR T-cell therapy entered remission after other therapies had failed. However, autoimmune and neurological side effects caused the suspension of several high-profile trials, and, in some cases, patient deaths.

Researchers are currently engineering “suicide switches” into the cells, which are genetically encoded cell surface receptors that trigger the cell’s death when a small molecule drug binds them. This is being done in an effort to increase the safety of CAR-T treatment. If a patient is having side effects, a doctor can give them a small-molecule drug, which will kill the cell within 30 minutes.

Other ways to keep people safe include making sure that CAR T-cells only attack cancer cells since healthy cells also have CD-19 receptors. Some scientists are attempting to improve the tumor recognition abilities of CAR-T cells by adding a second CAR, requiring the engineered cell to recognize two antigens before attacking.


A third approach to cancer immunotherapy is one that focuses on the mutated proteins that are characteristic of the disease. Neoantigens are the names given to the fragments of these mutated proteins that are displayed on the surface of cancer cells. Researchers are looking into ways to incorporate tumor-specific neoantigens into vaccines in order to assist the body in developing an immune response that is directed against cancer.

The findings of two recent, small clinical trials for patients with advanced melanoma suggest that neoantigen vaccines may be able to halt the progression of cancer, or in some cases, shrink the tumors, with relatively few adverse effects being reported. However, it is still too early in the clinical development process to determine whether or not the vaccines will lengthen the lives of cancer patients.

The production of a neoantigen vaccine requires two stages: the first stage involves locating mutated proteins that are specific to the majority of a patient’s cancer cells, and the second stage involves locating portions of those proteins that have the potential to most effectively stimulate an immune response.

Researchers will sequence the genome of cancer cells and then compare it to the sequence found in healthy cells in order to find proteins that have been mutated. After that, they determine which mutations result in the production of altered proteins and then look for those mutations. At the end of the process, they use computer models or cellular tests to determine which parts of proteins have the potential to be the most effective neoantigens.

The most difficult aspect of the process of creating a new neoantigen vaccine is the final step, which entails predicting the neoantigenicity of the vaccine. Confirming the activity of multiple neoantigens through laboratory experiments is time-consuming, and current computer models for predicting antigenicity have low validation and may be inaccurate.

Some fundamentals of cancer biology also complicate efforts to identify and create effective neoantigens for long-term treatment. The number of mutations in some cancers may be too high for neoantigen testing. Moreover, cancer cells continue to mutate as tumors expand, and not all cancer cells will express the neoantigens targeted by a vaccine. In order to avoid being attacked by the immune system, cancer cells may stop displaying antigens on the surfaces of their own accord. But finding these neoantigens can be a valuable tool in the fight against cancer.

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