Cancer immunotherapy is a field that has seen remarkable growth in the past decade. This growth is largely driven by some incredible stories of success. While immuno-oncology’s potential to provide treatments for even the most intractable cancers is high, a number of questions still exist, from exactly how to apply insights in the clinical setting to the actual efficacy of treatments for the whole patient population.
The following is a look at some of the most important questions and how experts have weighed in on them in the past months:
1. Can scientists make targeted immunotherapies work for more patients?
One of the most promising approaches to immuno-oncology involves the use of checkpoint inhibitors. This technique has gained significant traction since it was used to extend the life of former President Jimmy Carter. In some patients, these drugs are extremely effective, yet in other people they have little impact. Research has suggested that patients who respond the best are those whose immune systems already have a significant response to the cancer. For that reason, one approach might be stimulating an immune response within the tumor itself that checkpoint inhibitors can then boost. Existing drugs could accomplish this task, including chemotherapies that have been shown to have an immune-stimulating effect.
The question also comes with an important corollary: How can we tell who will benefit the most from checkpoint inhibitors? When people are fighting cancer, it is unwise to throw potentially toxic drugs at them that will have little effect. Thus, it is important to figure out how to identify the patients who will react best to the treatment and how to make the immunotherapy even more effective for them.
2. Does immunotherapy have the potential to prevent cancer?
Immuno-oncologists tend to think that immunotherapy does have the potential to prevent the development of cancer. However, this goal is a long-term one. Some cancer vaccines can prevent cancer by preventing the diseases that lead to them, but scientists are looking at more direct mechanisms. For example, researchers at the University of Washington will soon bring a potential vaccine to prevent breast cancer to early-phase clinical trials. The vaccine works by training the immune system to fight against a wide range of different cancer markers. In as few as three to five years, this sort of vaccine could be approved for clinical usage in women with high risk of developing breast cancer.
Progress in this regard will depend on learning more about the genomic signatures of precancerous growths, as well as the immune environments associated with them. Such a project will require concerted effort between several different organizations. However, the research would point to important biological targets for vaccines and might even reveal new immune-boosting strategies.
3. Do T cell therapies have applications against solid tumors?
The greatest success in T cell-based immunotherapies has been seen in blood cancers, which makes sense considering that the cancer cells are in the bloodstream and more accessible to immune cells. Tumors present special challenges because their microenvironments are designed to deactivate T cells, and the strategies used to do so vary across tumors. At the same time, researchers are actively looking for effective ways to deliver immunotherapies to solid tumors.
One potential strategy for adapting T cells to work in solid tumors is to teach them to interpret signals to shut down as instructions to become active. Researchers at Fred Hutch are pursuing this strategy, and they hope to begin preclinical testing within a year.
Biomarkers are another approach. By training T cells to target the right cells, scientists can make the immune attack significantly more effective. Advances in other technologies, such as quick and affordable genome sequencing, and proteomic arrays, are facilitating these efforts. This sequencing allows researchers to identify ideal biomarker targets.
4. What is the price tag of immunotherapy?
Because many of the immuno-oncology techniques require development of autologous therapies, the price tag for these treatments could become impedingly expensive. Some estimates have put the societal cost of new immunotherapies as high as $174 billion in the United States alone. T cell therapies are extremely complicated and initial costs will likely be very high, especially as the technology is being refined and scaled. However, this trend is not uncommon in biomedical sciences. For example, genome sequencing cost $100 million 15 years ago. Today, the technique is around $1,000. Similarly, the cost of cellular immunotherapies will likely drop substantially over time, especially as processes become easier and more refined.
The likely drop of prices makes it less helpful to think about the question in terms of the cost of treatment. Instead, the question should be about value. What does a patient receive for the cost of treatment? Treatments that offer a potential cure are obviously more valuable than life-extending therapies. Early indications show that T cell therapies have the potential for long-term disease control, meaning that they either cure a cancer or turn it into a chronic, but not life-threatening, condition. More research on this potential is necessary before a real value judgment can be made.