Immunotherapies
Immunotherapy is a fairly new approach for the treatment of malignancies, with many concepts and drugs still in the laboratory phase, or in transition from laboratory to pre-clinical trials, or some selected clinical trials in solid tumours such as lung cancer. For the treatment of head & neck malignancies, there are no clinically evaluated and established drugs or treatment schemes at this point in time (2018). However, the whole approach of utilising the body’s immune system to inhibit malignancies carries genuine promise. Accordingly, we discuss the approach in more detail and hope/expect that in the not too distant future the promise of finding selective immunotherapy treatments for malignancies without some of the major adverse effects of conventional treatments ( surgery, radiotherapy, chemotherapy) and not introducing other adverse effects, will be realised.
Immunotherapy utilizes the immune system to inhibit the growth and/or spread of cancerous cells. There are different ways to achieve this: it can be an active or a passive approach. Whilst active immunotherapy requires a working immune system, passive immunotherapy can be used even if the immune system is significantly weakened.
Active immunotherapy stimulates the immune system to recognise and attack malignant cells. Active immunotherapy creates an immunological memory and will thus have a lasting effect. Common forms of active immunotherapy include:
- vaccines;
- checkpoint inhibitors (agents that block proteins that stop the immune system from attacking malignant cells; of most potential promise if this translates to the treatment of head & neck cancer);
- adoptive cell transfer (transplantation of own or donated, genetically modified cells (mostly a particular type of white blood cells, T cells, that form part of the immune system).
Passive immunotherapy provides the immune system with external supportive agents to use, but this means that no immunological memory is created and the treatment must be administered multiple times. The main form of passive immunotherapy is using monoclonal antibodies (an antibody that is derived from a single type of cell line and typically is specialised to interact with a particular type of antigen; the approach has been discussed for about 30 years but still awaits major break-through success in clinical use for the treatment of malignancies).
Malignancies, such as squamous cell carcinoma (the most common type of head & neck cancers) have immunosuppressive properties (or, sometimes acquire such properties), so some immunotherapies tackle this suppression. The two main mechanisms that malignancies have for evading detection (and elimination) by the immune system are:
- to reduce the induction of an immune response (immunogenicity);
- to alter gene expression and hinder the production of some proteins that form part of the detection pathways that normally alert the immune system to the presence of invaders (in particular virus infections) or malignant cells.
Immunogenicity involves suppressing the signals of an immune response or sending ‘normal’ signals to immune checkpoints, therefore allowing malignant cells to ‘hide’ from the body’s inbuilt defence strategies.