Our personal cancer-killers
IMMUNOTHERAPY IS a new form of treatment which charges the patient’s own immune system to attack cancer cells, in addition to, or sometimes replacing, chemotherapy. Historically, “unselected” treatments for cancer, such as chemotherapy and radiotherapy, have been focused on damaging the DNA of cancer cells. However, this approach often resulted in intolerable collateral damage to other systems, with side-effects such as low white blood cells (neutropenia), sepsis and diarrhoea.
Tumours also frequently developed resistance to treatment. Immunotherapy has been explored since the late 19th century but, due to the complexities of cancer biology being poorly understood, this resulted in decades of failure.
This failure is beginning to reverse, with major breakthroughs in understanding a subgroup of blood white cells called the T-cells (T-lymphocytes).We now know more about their responses, their interactions with tumours and the micro-environment the tumour cells inhabit and we can identify receptors that can be switched “on” or “off”, allowing the immune system to recognise cancer proteins and ultimately enabling the T-lymphocytes to eliminate cancer cells.
Among the immune therapies already available, or becoming available, for cancer are monoclonal antibodies, vaccines, checkpoint inhibitors, TILs and CAR T-Cells, all explained below. MONOCLONAL ANTIBODIES These antibodies adhere to a molecule on the surface of the cell called an antigen and can bring about its destruction. They can be designed to target antigens found on cancer cells.
The most well-known have been used for several years, for example Herceptin in breast cancer and Rituximab in non-Hodgkin’s lymphoma.
Newer “bi-specific” monoclonal antibodies are constructed from two different antibodies, one of which attaches to the antigen on the cancer cell and the other to a protein on an immune T-cell. This joins the cancer cell with its potential destroyer. VACCINES For many years, researchers have been trying to develop vaccines for cancer but this has proved difficult. Today, vaccines are often linked to facilitating molecules called adjuvants, which help boost the body’s own immune response and might help the vaccines work better.
Vaccines can be made from tumour cells themselves, altered and killed in the laboratory, then injected back into the patient, the immune system then destroying these cells and any other remaining living cancer cells in the body. Vaccines from immune cells, called dendritic cell vaccines, are the most promising. These are cells that normally help the body’s immune system recognise cancer. Provenge, a treatment for advanced prostate cancer, is an example of a dendritic cell vaccine and is one of the more successful. CHECKPOINT INHIBITORS These drugs can unleash an immune attack on cancer cells. Normal immunesystem T-cells patrol the body constantly for signs of disease. If a cell is normal and healthy, the T-cell leaves it alone but if it is abnormal, such as a cancer, the T-cell will then lead an attack on that specific cell. Checkpoints are proteins which control this function. Cancer cells often use checkpoint molecules of their own to evade the immune system and allow the cancer to grow. But checkpoint inhibitors block these molecules on cancer cells and allow the normal immune cells to function again and eliminate the cancer.
Checkpoint inhibitors are the great new hope of cancer therapy. The major checkpoint proteins discovered so far are PD-1 and CTLA-4.
Targeting these checkpoints with antibodies is quickly becoming an important part of the treatment for some cancers. Two of these antibodies — nivolumabandpembrolizumab—have