T cell-directed cytokine therapy has shown very promising results in some patients with leukaemia. These results in combination with some animal model data gives a big hope that T cells can be used to trigger anti-tumour response.
How does this work?
There are 2 approaches:
- Protein antigens expressed by tumours are degraded in the cytosol and peptides derived from the proteins are incorporated into major histocompatibility complex (MHC) which are then expressed on the cell surface. The peptide in MHC is then recognised by specific T cell (if these T cells exist).
- In the second approach patients are vaccinated against tumour-specific antigens in order to trigger immune reaction.
However, some preliminary data has shown that such approach triggers immunological response but not clinical response.
In melanoma it was observed very good response from patients. This led to the hypothesis that all tumour cells express antigens that could be attacked by T cells.
But is there universal tumour antigen?
The idea behind this approach is to identify tumour antigen which is specific for all tumours and use it to trigger immune response. This method is known as reverse immunology. In real life the immune response to tumour cells in very weak or absent.
In order to find such universal antigen it has to meet the following criteria:
- It has to be expressed by majority of human cancers
- It has to have peptide sequence that bind to MHC molecules
- It has to be processed by tumour cells
- It has to be recognized by T cells in a MHC-restricted fashion
Are there any potential tumour antigens?
Telomerase regions like HLA-A2, -A3 or -A24 are expressed by more than 75% of cancer patients, which means that nearly three quarters of all cancer patients could be considered for hTERT-specific therapies. What is specific to molecules like hTERT is that they are specific to tumour cells and naturally presented by MHC. However small mutations in targeted epitomes could be a problem as they won’t be recognised by the immune system.
Identifying universal tumour-associated antigen could be a big step towards preventive immunotherapy. One of the challenges is that vaccination in patients who already have cancer will not be efficient. However, this should not discourage all the efforts in this area because prevention is important part of cancer management.
Author: Olga Peycheva
Olga is a clinical research professional who has been working in clinical research since 2005. She has extensive experience in clinical research in Eastern and Western Europe.
Originally published on 1 Sep 2020