Targeting non-coding RNAs to boost immunotherapy response in cancer

Suitable for Honours and PhD students

Immunotherapy has emerged as a transformative mode of cancer therapy. However, a number of cancer-types do not respond to immunotherapy, and a significant proportion of cancer patients who initially show response develop resistance later in their treatment. Therefore, development of novel approaches to boost immunotherapy response are needed in order to extend the proportion of patients benefiting from immunotherapy. Non-coding RNAs provide the potential to encode novel neoantigens that could be recognised by T cells. Immunopeptidomic studies indicate that many non-coding RNA-derived proteins make up a major source of tumour neoantigens. Increasing the level of these proteins by modulating the expression of non-coding RNAs has the potential to enhance immunotherapy response in cancer.

HYPOTHESIS

Increasing peptides encoded by non-coding RNAs by targeting epigenetic mechanisms enhances immunotherapy response in cancer.

AIMS

To develop novel approaches in enhancing the expression of neoantigens and identification of non-coding RNAs that encode tumour neoantigens that trigger T cell response in cancer.

APPROACH

1. Immunopeptidomic analysis.
2. Proteogenomics analysis on non-coding regions of the genome.
3. DNA and RNA editing using CRISPR-mediated approaches.