How does Car-T work. Credit: @CireniaSketches / CNIO.
What is cancer immunotherapy?
Immunotherapy is a therapeutic tool based on enhancing the ability of the patient’s immune system to identify and destroy cancer cells. It is a broad concept that encompasses various strategies. The immune system, our body’s defenses, is prepared to fight external aggressions (bacteria, viruses, fungi and toxins) and internal ones, such as tumor cells. But it is not perfect, and cancer cells can “trick” the immune system so as not to be detected.
Why is it currently booming?
The immunotherapy boom began with the approval, at the beginning of the last decade, of ipilimumab, against advanced melanoma. This is a monoclonal antibody from the family of so-called ‘checkpoint inhibitors’ of the immune system: it removes the brake that the body naturally puts on its own defenses, and thus boosts the attack on tumor cells. In 2016 immunotherapy was chosen as the therapeutic advance of the year in oncology. Since then, research has multiplied. There are numerous clinical trials testing the various ways of using immunotherapy, in various tumors. Overall, the results so far suggest that it is an increasingly promising option.
Is immunotherapy research moving forward?
For Luis Álvarez-Vallina, a researcher at the Spanish National Cancer Research Center (CNIO), there is no doubt that “immunotherapy is the basis of future medicine. In the last decade immunotherapy has established itself as the great option in cancer, capable of obtaining responses that had not been seen before in oncology,” he adds. And he also highlights the advances in research: “The current clinical development is amazing.”
What are the main types of immunotherapy?
There are several ways to induce the immune system to identify and fight cancer cells.
So-called checkpoint inhibitors, such as ipilimumab, remove the brake that the body naturally puts on its own defenses (to avoid attacking itself); by removing these brakes, the defensive cells can attack tumor cells with full force. Drugs of this type are working in 20% to 30% of people with solid tumors.
Against hematological cancers, however, the most advanced system are cell therapies. In these, the patient’s lymphocytes (defense cells) are modified in the laboratory so that, once re-infused in the person, they can locate and eliminate tumor cells much more effectively. The best-known cell therapies are called CAR-T, approved to treat six types of hematological cancers (one type of multiple myeloma and several types of lymphomas and leukemias).
What exactly are CAR-Ts?
In CAR-T therapy, T-lymphocytes are extracted from the patient’s blood to be treated and modified in the laboratory. The modification allows the person’s T-lymphocytes to recognize exactly which tumor he or she is suffering from by making them able to identify a specific protein on the surface of these precise cancer cells. Once modified, they are multiplied, also in the laboratory, and reintroduced into the patient’s body to destroy the cancer cells.
Will we have cancer vaccines?
The term ‘cancer vaccine’ usually refers to therapeutic vaccines, i.e. their aim is not to prevent, but to cure.
Much of the most advanced cancer vaccine research is based on messenger RNA technology, the same technology that produced two of the covid vaccines. Two are now in advanced trials: one from Moderna to treat melanoma; and one from BioNtech to treat lung cancer. Both compounds could be available by 2030, both companies have announced.
Which cancers are treated with immunotherapy?
At present not all cancers can be treated with immunotherapy. Those that have shown the best results with the different types of immunotherapy are: melanoma, lung, kidney, bladder, stomach, liver, head and neck, some gynecological tumors and lymphomas. But research is being carried out on practically all types of cancer.
Why immunotherapy does not work the same in all types of cancer
Immunotherapy works better in some cancers than in others, and the same is true for individual patients. Understanding why this is so is one of the main objectives of current research in this area. Two aspects must be taken into account. The first is that immunotherapy is not like a drug that is prescribed to anyone suffering from any type of tumor. It is a personalized treatment, which is produced specifically for a particular tumor in a particular patient. In almost all cases, immunotherapy is applied as a last option, in patients in whom other therapies have failed.
Why is immunotherapy expensive?
The very basis of immunotherapy is what makes it an expensive treatment. Whether through monoclonal antibodies, cellular immunotherapy or vaccines, immunotherapeutic tools are based on fighting a specific tumor, the one specific to the patient to be treated.
No two tumors are alike, and immunotherapy requires an in-depth analysis of the characteristics of each tumor and even of the microenvironment surrounding it. It is then necessary to design the appropriate strategies and tools to combat that specific tumor. As it is not a standard treatment applicable equally to all patients, as is the case with any conventional drug, the costs rise considerably.
What are the main lines of research in immunotherapy?
Research in immunotherapy against cancer is in full swing. Dozens of scientific groups around the world are investigating the different aspects of this therapy. The main lines of research are:
- Non-responsive cancers. One of the key questions in the advancement of immunotherapy is to understand why some cancers are resistant to immunotherapy. And one of the solutions being investigated is the combination of various immunotherapies or of immunotherapy with other oncological therapies, such as chemotherapy, targeted therapies or radiotherapies, among others.
- To find ways to predict the response to immunotherapy, through the identification of biomarkers.
- To better understand the relationship of cancer cells with the immune system. Understanding the mechanisms by which cancer cells are able to escape the immune system (immune evasion) may lead to the identification of drugs capable of blocking these processes.
- Advancing the different types of immunotherapy. There is a multitude of research underway that delves into the different tools used in immunotherapy. An example of this line is the work carried out by Luis Álvarez-Vallina’s group, which represents an advance in CAR-T therapy for the treatment of multiple myeloma, some types of leukemia and lung cancer.
Álvarez-Vallina’s group has developed a new strategy to modify T lymphocytes using a proprietary technique called or STAb-T cells. The work is in different phases of research in each of the tumor types they are working with. In the case of multiple myeloma, they plan to start a human clinical trial in 2025.
Latest results of the Spanish National Cancer Research Center (CNIO) in immunotherapy:
CNIO researchers propose a new treatment for brain metastasis based on immunotherapy
A new form of immunotherapy to treat solid tumours shows therapeutic potential in animal models