Cancer is the second leading cause of death for adults in the United States. Defined as the condition in which the body’s cells divide uncontrollably, cancer remains infamous for being an aggressive disease to tackle. For decades, the core treatments for cancer have been chemotherapy, radiation, and targeted surgery. However, researchers recently began developing a novel method of fighting cancer known as immunotherapy. This method works by employing the power of a patient’s immune system, which can be suppressed or amplified depending on the given situation, to combat specific diseases. A more refined immunotherapy approach for fighting cancer is called adoptive cell transfer.
Adoptive cell transfer is defined as the process in which a patient’s T-cells, which identify and chemically mark foreign substances, are engineered to recognize and attack tumors that are typically caused by cancer. CAR T-cell therapy gets its name from the chimeric antigen receptors (CARs), which are produced on the T-cell via genetic engineering. These receptors are essentially the parts of the system that allow the cancer fighting mechanism to initiate, as they receive specific signals from the cancerous tumors, triggering the process. Utilizing chimeric antigen receptors for T-cells to fight cancer sparked excitement among the scientific community.
The process begins when the T-cells are collected from the patient via apheresis, a procedure in which blood is withdrawn from the body and separated into its different components, including plasma, platelets, and white blood cells. The extracted T-cells are then sent to a laboratory where they are genetically engineered by scientists to produce chimeric antigen receptors on their surface. In order to produce these chimeric antigen receptors, viral vectors are used to incorporate the desired gene into the patient’s genome, and this DNA segment codes for its production. Next, the CAR T-Cells are multiplied until there are millions of them, and are finally infused back into the patient.
When the CARs comes into contact with a cancerous tumor’s chemical trail, specific effectors are activated, giving the T-cell the signal to attack the tumor cell. While normal immune cells would still be able to attack cancer cells on their own without CAR engineering, CAR T-cell engineering increases the efficiency and speed of the process as a whole.
So far, CAR T-cell therapy has mostly only been used to treat patients with leukemia, or blood cancer. Several trials have been carried out in which this treatment approach was tested in several patients diagnosed with advanced acute lymphoblastic leukemia (ALL), and results show that their cancers had disappeared almost entirely after treatment. Furthermore, these same patients remained cancer-free for extended periods of time, showing that this form of therapy shows signs of remission, or diminished symptoms of cancer.
Although CAR T-cell therapy seems scientifically legitimate and takes on a never-seen-before approach to treating cancer, it has so far strictly been used in clinical trials. This cancer treatment has been succeeding for the most part—initial tests for CAR T-cell therapy have produced sufficient positive results to foster optimism that it could become a real solution to cancer in the near future. However, the alarming side effects have deterred this therapy from becoming procedure in hospitals around the world; scientists are currently working to counterattack these effects.
While this therapy is extremely promising, there are some issues about it that must be addressed before its wide implementation. The first issue with this therapy is that manufacturing is complicated. In order for the process to run smoothly, the extracted CAR T-cells must be multiplied and expanded to a population of at least one million. The manufacture of personalized T-cell therapies cannot be done on an industrial scale, as this specific process requires large amounts of equipment and attention to each individual case, and as such is extremely expensive. Cytokine release syndrome is another major complication of this procedure. When the engineered T-cells are infused back into the patient, high amounts of cytokines, or chemical messengers, are released into the bloodstream all at once. This rush of chemicals results in symptoms including high fever, hypotension, fatigue, and neurotoxicity. In July of 2016, three patients in a Juno Therapeutics clinical trial died from the complications of neurotoxicity arising from CAR T-cell therapy.
Not only does the CAR T-cell therapy cause the immune system to go haywire, it can in some cases act conversely by suppressing the immune response. When the body experiences the adoptive cell transfer, T-cells are engineered to attack tumors. One worrisome side effect of this therapy is that CAR T-cells could attack all immune cells, regardless of whether they are cancerous or healthy, resulting in a condition known as B-cell aplasia. This condition suppresses the immune response, making the body more susceptible to diseases.
Although the process of CAR T-cell therapy has been successful for the most part, multiple side effects such as cytokine release syndrome and B cell aplasia occur as patients undergo this form of immunotherapy. Researchers are currently working to counterattack these side effects and to produce a superior T-cell defense mechanism. The positives of CAR T-cell therapy far outweigh any negatives, and researchers are pushing to reduce the cost and risk associated with the procedure in order to see it into mass use, where it will undoubtedly revolutionize the field of cancer treatment.