Personalised cancer vaccines
| ISRCTN | ISRCTN58774519 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN58774519 |
| Secondary identifying numbers | 16/LO/1512 |
- Submission date
- 15/08/2016
- Registration date
- 22/09/2016
- Last edited
- 28/09/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English Summary
Background and study aims
Pancreatic cancer causes the uncontrolled growth of cells in a large gland of the digestive system. Pancreatic cancer has a very poor prognosis (forcast) with an overall survival rate of less than 5%. Current treatments are ineffective and even if the patient responds to initial treatments, relapse (the cancer coming back) is common due to the survival of small populations of resistant cancer cells. The immune system is capable of recognising and eliminating invading organisms by virtue of differences in their appearance when compared to normal components of the body. Cancer cells also have a different appearance compared to normal cells. However, these differences are often too small and weak to stimulate the immune system sufficiently to respond effectively to eliminate the tumour. The aim of this study is to analyse the small differences between healthy and cancer cells in pancreatic cancer patients by analysing genetic information from pancreatic cancer cells and see their ability to stimulate an immune response.
Who can participate?
Adults aged 17 to 66 who fulfill the NHS blood donation requirements.
What does the study involve?
Blood samples are taken from participants and are analysed for genetic information with respect to their ability to stimulate an immune response against cancer.
What are the possible benefits and risks of participating?
Not provided at time of registration.
Where is the study run from?
1. NHS Blood and Transplant. Blood Donation Centre Edgware (UK)
2. NHS Blood and Transplant. Tooting Blood Donor Centre (UK)
When is the study starting and how long is it expected to run for?
August 2016 to July 2018
Who is funding the study?
Pancreatic Cancer Research Fund (UK)
Who is the main contact?
Professor Yaohe Wang
Contact information
Public
Charterhouse Square
London
EC1M 6BQ
United Kingdom
Study information
| Study design | Observational |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | Other |
| Study type | Screening |
| Participant information sheet | Not available |
| Scientific title | Identification of immunogenic neo-epitopes for the development of personalised pancreatic cancer vaccines |
| Study hypothesis | Sequence analysis has allowed us to develop a peptide library of neo-epitopes that are expressed at high frequency in patient populations and have high binding affinities compared to their wild-type counterpart to HLA-A2, HLA-DP4, HLA-E*01:01 or HLA-*01:03 molecules. We hypothesise that a number of these will be sufficiently immunogenic to stimulate a T cell interferon-γ (IFN-γ) response in vitro, that will translate to an in vivo anti-tumour response. Immunogenic neo-epitopes can then be combined in a peptide vaccination program using adjuvants such as oncolytic viruses for targeted delivery and expression within tumours of PDAC patients to stimulate robust and long-term anti-tumour responses. |
| Ethics approval(s) | The Proportionate Review Sub-committee of the London - Westminster Research Ethics Committee, 10/08/2016, ref: 16/LO/1512 |
| Condition | Pancreatic cancer |
| Intervention | Peripheral blood mononuclear cells (PBMCs) obtained from leukocyte filters from healthy individuals will be HLA typed using commercially available reagents from thermofisher scientific. HLA-A2, HLA-DP4, HLA-E*01:01 and/or HLA-E*01:03 positive samples will be pulsed with peptides selected after bioinformatics analysis of available sequence data. IFN-γ and interleukin-2 (IL-2) production by the T cells in the samples will be evaluated by ELISA after two rounds of stimulation within a two weeks time as a measure of peptide immunogenicity. Once immunogenic peptides have been identified, their wild-type counterparts will be analysed in parallel to confirm specificity for the mutated epitope. Immunogenic peptides whose wild-type counterparts do not elicit immune responses will then be selected for inclusion in an oncolytic virus-based vaccine to be analysed in vivo using transgenic HLA-A2/HLA-DP4 mice. |
| Intervention type | Other |
| Primary outcome measure | Immunogenicity of neo-epitope candidates selected from available mutanome data using peripheral blood mononuclear cells (PBMCs) from healthy individuals. |
| Secondary outcome measures | N/A |
| Overall study start date | 01/08/2016 |
| Overall study end date | 20/07/2018 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | About 100 individuals. |
| Participant inclusion criteria | Individuals who fulfill the NHS BT requirements for blood donation, which are: 1. fit and healthy 2. weigh over 7 stone 12 lbs or 50kg 3. are aged between 17 and 66 (or 70 if you have given blood before) 4. are over 70 and have given blood in the last two years |
| Participant exclusion criteria | Same as NHS BT criteria, which are: 1. receiving treatment 2. taking medication 3. travelling outside of the UK 4. tattoos 5. pregnancy 6. illness 7. cancer 8. received blood, blood products or organs |
| Recruitment start date | 01/08/2016 |
| Recruitment end date | 20/07/2018 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Burnt Oak Broadway
Edgware
Middlesex
HA8 0AD
United Kingdom
Tooting
London
SW17 0RB
United Kingdom
Sponsor information
University/education
5 Walden Street - Lower Ground Floor
London
E1 2EF
England
United Kingdom
"ROR" |
https://ror.org/026zzn846 |
|---|
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- PCRF
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 20/07/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | The results of this study will be published in suitable peer-reviewed scientific journals. |
| IPD sharing plan | - |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 27/05/2022 | 28/09/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
28/09/2022: Publication reference added.
06/06/2017: Plain English summary added.
10/04/2017: Internal review.
