When we compare cells from two different people, they are not the same. This is also true about tumor cells, they may share some characteristics, but no two tumors are the same. “Personalized medicine” is based on this exactly because we can sequence and study individuals tumors to customize therapies that are equipped to fight that specific tumor. There are two target cells for these therapies and they are T-cells, which are involved in both marking and killing infected or cancerous cells, as well as dendritic cells, which act as a bridge between innate and adaptive immune responses. If we are able to design treatments that effectively activate and train these cells to target specific diseased cells, the therapeutic benefits would help save millions of lives, ranging from those with cancer to others with autoimmune diseases and even HIV.
Several trials are being conducted to develop new chimeric antigen receptor T-cell (CAR-T) therapies. A study at the Institute for Advanced Medical Research in Japan is working on mice models to test human CAR-T therapies, but they have observed promise in a specific CAR-T therapy in mice with solid tumors with no adverse side effects (Kato, n.p.) Kato and his team have genetically engineered T-cells to target the antigen glycipan-1 (GPC1). This antigen is found in high levels in tumor cells, but not in normal cells, which is why no adverse effects have resulted from this potential cancer treatment. In order to move into human clinical trials, the team is working on developing new models to show both the effectiveness and safety of this CART-therapy.
The most common side effect of these therapies, especially once the CAR-T cells have started to multiply in your body is cytokine release syndrome (CRS), marked by fever and low blood pressure. It is a double-edged sword as CRS takes a toll on the patients themselves, but is a sign that the CAR-T cells have started their work, producing cytokines to activate effector cells to destroy their targets (Thibodeaux, n.p.) This is one example of adverse effects called “on-target/off-tumor toxicity,” which results when CAR-T cells attack normal, healthy cells that are presenting their target antigen (Thibodeaux, n.p.). This is why the study I discussed in the previous paragraph is so impressive because it is increasing the safety of this therapy while still maintaining the therapeutic effect. Aside from these health concerns, another obstacle for these therapies is cost. Two specific therapies, tisagenlecleucel and axicabtagene ciloleucel, are over $373,000, and that is for just one infusion (Locke, Lin, n.p.) “While we know the high list prices of CAR T-cell therapies, we also know that there is a high cost to administering them. Unfortunately, the U.S. medical system appears to have a bureaucratic inability to actually deliver the dollars where they belong (Locke, Lin, n.p.).” Yet again, people who are suffering from life-threatening diseases must choose between dying and going into tremendous amounts of debt to receive a treatment that may or may not work for them. It is a visionary therapy, but it also sheds light on one of the biggest problems of the US health system.
Jaylin’s Thoughts: Microbiology 