PROTEAN: Proteomic Profiling of Oesophageal Adenocarcinoma Neoantigens
Research type
Research Study
Full title
PROTEAN: Proteomic Profiling of Oesophageal and Gastroesophageal Junction Adenocarcinoma Neoantigens
IRAS ID
309452
Contact name
Russell Petty
Contact email
Sponsor organisation
University of Dundee and Tayside Health Board
Duration of Study in the UK
1 years, 0 months, 30 days
Research summary
Summary of Research:
People with oesophageal (gullet) and gastroesophageal (stomach/gullet) cancers receive treatments such as, chemotherapy, radiotherapy and surgery, but often they are not effective in curing the cancer. Scientists and doctors are working together to make develop new immunotherapy treatments, immunotherapy helps the immune system fight cancer. There are some immunotherapy treatments for oesophageal and gastroesophageal cancers, but they only work in a small number of people.
There are markers in the cancer cells which can sometimes tell which immunotherapy will work best for a person, called neoantigens. To be able to develop more immunotherapy treatments we first have to find out which neoantigens are in oesophageal and gastroesophageal cancers.
This study will collect cancer tissue samples from people with oesophageal and gastroesophageal cancer. Scientists at Platinum Informatics Ltd will look at the cancer tissue to identify neoantigens.We will also examine connections with the results from blood samples, the neoantigens and cancer progression.
We hope to use any neoantigens identified to develop new, more effective immunotherapies. This would allow a personalised approach to the use of immunotherapies.
Summary of Findings:
In the PROTEAN study we aimed to characterise the expression of proteins on the surface of oesophageal cancer cells that could be recognised by the immune system and hence be targets for cancer vaccines - a new treatment approach that aims to harness patients own immune system to control or eliminate their cancers and which has shown promising results but is dependent upon identifying the best possible targets, known as tumour specific antigens or neoantigens for the vaccines on the tumour cell surface. Current approaches identify these targets indirectly by inferring what they might be form gene mutations or the over expression of genes in cancers- this technique is known to be inefficient with o less than 1 in 10 neoantigens identified actually ending up being useful targets for cancer vaccines. We aimed to evaluate a new technique-mass spectrometry based immunopeptidomics that directly profiles the neoantigens themselves at the tumour cell surface- we hypothesised it would be more efficient than current approaches but it was uncertain if mass spectrometry base immunopeptidomics would be possible on small biopsies of tumours that available from routine diagnostic biopsies of Oesophageal cancer and hence whether it could be used in practice. In PROTEAN we obtained tumour biopsies from 86 patients with oesophageal adenocarcinoma and demonstrated that immunopeptidomics was successful in all cases 100%, thereby demonstrating that it is possible to perform this technique on routinely available diagnostic small tumour biopsies. The results also demonstrated that while there is some overlap the majority (>90%) of neoantigens on each patients are unique to that patients tumour- this suggests that in order to be the most effective they can be cancer vaccines may need to be personalised to the neoantigen targets present in each patients tumour. Interestingly we found that 19/20 neoantigens identified by immunopeptidomics would not have been identified by current approaches based on analysing gene mutations or gene expression ( RNAS Seq) thereby demonstrating that immunopeptidomics appears to be a much more efficient way of detecting neoantigens . In summary this study has demonstrated the feasibility and usefulness of a new technique to identify targets for cancer immunotherapies including cancer vaccines, that is much more efficient at identifying the needed targets and we have described for the first time the neoantigen profiles of oesophageal adenocarcinomas, and how they vary from one patient to another . This will enable immunopeptidomics to be investigated further to accelerate the development of new more effective cancer immunotherapy treatments especially cancer vaccines including those personalised precisely against each patient tumour.REC name
Wales REC 6
REC reference
22/WA/0223
Date of REC Opinion
19 Aug 2022
REC opinion
Favourable Opinion