T cells, antibodies, immune defences - concepts we have learnt more about after a couple of years of a global Covid-19 pandemic. Understanding of how the immune system works against cancer is another major issue for research and development of new treatments.
‟Antibodies have been used in cancer care for close to 25 years but it is over the past five years that new techniques and treatments have taken a new direction", says Mats Jerkeman, consultant physician in oncology at Skåne University Hospital and professor of clinical oncology at Lund University.
New knowledge about how the body's cells can be reprogrammed to attack their assailants gives hope to a rising number of patient groups. New techniques are being tested to enable more patients and more types of cancer to be treated effectively with fewer side-effects, and several drugs are already in use.
One way of speeding up the immune response against cancer is to use antibodies. These are proteins that are part of the immune system, but they can also be produced outside the body and administered in the form of drugs. Mats Jerkeman explains the progress in the new forms of treatment and how patients are affected:
‟For the treatment of certain types of breast cancer and lymphoma, antibodies have been used for two decades. The first generation of antibody treatments consists of an antibody targeted at something on the surface of the tumour cells. Another type of antibodies that are very effective and have now been used for several years are those that activate the immune response and have revolutionised the treatment of malignant melanoma."
Smarter antibodies
Currently, developments are underway towards new types of antibody-based treatments. They are much more effective and are steadily becoming smarter. One method entails linking antibodies to chemotherapy drugs, a form of treatment that is toxic to the cancer cells and stops their growth. What is different about the new antibodies is that they bind to the tumour cells and penetrate them, whereupon the chemotherapy molecules are released and kill the cancer cells.
The challenge is to find new surface proteins or antigens, which are good targets. It is important to find the right antigen so that the drug does not kill healthy cells, which it potentially could.
Engaging T cells
Another use of new antibody technology is based on making antibodies with one part that binds to the tumour cell and another to the immune defence cells, above all those known as T cells. That enables the tumour cells to be physically linked to the immune defence cells. When these two come close to one another, the immune defence cells are activated and kill the tumour cells; the T cells are engaged.
‟There is currently a rapid development of molecules that work in this way", continues Mats Jerkeman. "This is good news for the treatment of lymphoma, various types of blood cancer and prostate cancer".
Researchers are now ensuring that the immune system's cells are drawn towards the tumour cells, after which they do the work. At Lund University, researchers are taking part in several clinical trials of this type of bi-specific antibodies or T cell-engagers and the results have been impressive.
Reprogramming the immune system
Alongside antibody technology, cell-based drugs are a very successful area. A first class of drugs of this type that is much discussed is known as CAR-T cells. The principle of this treatment is to remove or harvest the patient's immune defence cells, or T cells. A virus is used to insert a gene into these cells which then start to develop a protein on their surface.
This protein is not normally present in humans but is entirely a designed, synthetic protein. It has an outer part which binds to an antigen on the tumour cell's surface, and an inner part which activates the T cells to become aggressive.
‟In simple terms, you can describe CAR-T as reprogramming the body's own T cells. The patient's white blood cells are collected and sent to a special laboratory. In this factory, the cells are developed and once they are ready, they are sent back to the hospital. There, they are administered intravenously to the patient", explains Mats Jerkeman.
Inside the body, these cells attack the tumour cells very efficiently. This treatment has proven not only to alleviate but even to cure cancer. There are already a few registered drugs using this form of treatment.
So is there only good news for patients? This is true to a large extent but this form of treatment can activate the immune system very powerfully. It can cause high fever, lower blood pressure and require a stay in hospital for some time. For some patients, the reactions may require intensive care.
Another problem is that it is currently a very expensive treatment but the prognosis is that more patients will eventually be able to be treated with this method nevertheless. At present, Mats Jerkeman and his colleagues in Lund have access to one product based on CAR-T cells to treat lymphoma, and one for myeloma, within a clinical trial.
Donated cells
Currently, the patient's own T cells are used in the treatment. It takes up to four weeks to cultivate these cells, which can be a long time in the context of an aggressive form of cancer. Now, variants are emerging which use donated cells. A donor can give this type of cell to many different patients, eliminating the wait for individual production of cells for each patient.
Cells from a donor can be prepared and frozen, for retrieval when needed. It is also possible to cultivate tissue cells in a laboratory to be transformed into T cells. A further alternative is to use another type of cell, known as Natural Killer cells. They are considered to be even more effective as well as causing fewer side effects.
‟This is an exciting time to be involved in cancer treatment", observes Mats Jerkeman, ‟and we are only at the beginning of this development. This is a hot topic both for us as researchers and clinicians, and for patient groups and the interested general public. We are learning an incredible amount all the time."
