Vaccine and Immunomodulatory Strategies to Target the Cancer Mutanome
Lead Research Organisation:
University of Southampton
Department Name: Cancer Sciences
Abstract
Skills Priority Alignment: Quantitative Biology
Cancer immunotherapy covers a wide range of approaches that seek to equip the immune system to identify and eliminate tumour cells. Used in isolation, these approaches show promising results in improving tumour clearance and survival, however they are often limited by the ability of tumour cells to rapidly evolve mechanisms that aid immune evasion and tumour progression. We seek to focus on amplifying the differences between healthy and malignant cells, and explore the use of combination immunotherapy to target multiple pathways and achieve effective anti-tumour immunity.
Cancers are characterised by uncontrolled cell growth that is primarily driven by acquired somatic mutations in the genome. Next generation sequencing (NGS) approaches have helped mutations in protein-coding, exonic regions that generate neoantigens that are not encoded by the germline genome. These tumour specific antigens are ideal targets for immunotherapy as they have not been subject to immune intolerance mechanisms.
The increased protection and survival seen in preclinical melanoma models receiving neoantigen-specific RNA and peptide vaccines has been translated in the clinic. However, this vaccine-based approach required subsequent treatment with PD-1 blockade, indicating that vaccine-based combination immunotherapy with immune checkpoint inhibitors can potentially help establish lasting anti-tumour immunity. Therefore, this project seeks to develop vaccine-based immunotherapeutic strategies to target the mutanome in both a solid tumour (Head and Neck Squamous Cell Carcinoma (HNSCC)) and a lethal haematological malignancy (Multiple Myeloma (MM)).
Cancer immunotherapy covers a wide range of approaches that seek to equip the immune system to identify and eliminate tumour cells. Used in isolation, these approaches show promising results in improving tumour clearance and survival, however they are often limited by the ability of tumour cells to rapidly evolve mechanisms that aid immune evasion and tumour progression. We seek to focus on amplifying the differences between healthy and malignant cells, and explore the use of combination immunotherapy to target multiple pathways and achieve effective anti-tumour immunity.
Cancers are characterised by uncontrolled cell growth that is primarily driven by acquired somatic mutations in the genome. Next generation sequencing (NGS) approaches have helped mutations in protein-coding, exonic regions that generate neoantigens that are not encoded by the germline genome. These tumour specific antigens are ideal targets for immunotherapy as they have not been subject to immune intolerance mechanisms.
The increased protection and survival seen in preclinical melanoma models receiving neoantigen-specific RNA and peptide vaccines has been translated in the clinic. However, this vaccine-based approach required subsequent treatment with PD-1 blockade, indicating that vaccine-based combination immunotherapy with immune checkpoint inhibitors can potentially help establish lasting anti-tumour immunity. Therefore, this project seeks to develop vaccine-based immunotherapeutic strategies to target the mutanome in both a solid tumour (Head and Neck Squamous Cell Carcinoma (HNSCC)) and a lethal haematological malignancy (Multiple Myeloma (MM)).
Organisations
People |
ORCID iD |
Natalia Savelyeva (Primary Supervisor) | |
Cinderella Jawahar (Student) |
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
MR/N014308/1 | 01/10/2016 | 30/09/2025 | |||
1820185 | Studentship | MR/N014308/1 | 01/10/2016 | 31/03/2021 | Cinderella Jawahar |
Description | Meet the Scientist Sessions - LifeLab Southampton (ongoing) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Meet the Scientist events are run by LifeLab Southampton and involve presenting your research to school children between Years 7-11 or sixth-formers. Each session usually lasts around 15 mins, with around 10 students, where researchers present their work, and engage in a discussion with the students about the research area, and a career in science. Presenting my research and engaging in conversations about cancer and immunotherapy with these students led to many fruitful discussions and even debates about the use of animals in research. This is an ongoing engagement activity that I am involved with. |
Year(s) Of Engagement Activity | 2019,2020 |
Description | Oral Presentation at the Cancer Sciences Unit Conference 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Selected to deliver an oral presentation at the Southampton Cancer Sciences Unit Conference in October 2019. I presented a 15 min talk on my research and had the opportunity to engage with other academics and clinicians in discussion. |
Year(s) Of Engagement Activity | 2019 |
Description | Poster presentation at CIMT 2018 Annual Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presented a poster on Doggybone DNA vaccines at the CIMT 2018 Annual Meeting held in Mainz, Germany. I had the opportunity to speak to many academics and clinicians about my research and the results presented |
Year(s) Of Engagement Activity | 2018 |
Description | Poster presentation at the 10th Cancer Sciences Unit Conference 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Presented a poster on targeting the mutanome in multiple myeloma at the 10th Cancer Sciences Unit Conference in Southampton. Engaged in discussion with other academics. |
Year(s) Of Engagement Activity | 2018 |
Description | Poster presentation at the BACR Student Conference 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Presented a poster on targeting the mutanome in multiple myeloma at the BACR Student Conference in 2018. Engaged in discussions about my research with other PhD students from around the country. |
Year(s) Of Engagement Activity | 2018 |
Description | Poster presentation of Systems Biology at the Wessex Immunology Group Annual Spring Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Presented a poster on the work I had done during my second rotation at the Wessex Immunology Group Annual Spring Meeting. The event was titled 'Predictive Immunology: From Single Biomarkers to Omics' and therefore I presented a poster on a systems biology approach to understand T cell activation. I had the opportunity to engage in discussion with attendees and won best poster. |
Year(s) Of Engagement Activity | 2017 |
Description | Speaker at Pint of Science 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Speaker at the Pint of Science festival in May 2019. I had the opportunity to give a 15 minute talk on my research to the general public and engage in a discussion with them afterwards about cancer immunotherapy. |
Year(s) Of Engagement Activity | 2019 |
URL | https://pintofscience.co.uk/event/cancer-today |