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Background
Designing of immunotherapeutics, utilising patient derived dendritic cells generated
hope for personalised melanoma vaccine. To provide sufficient immune signals, these
dendritic cells are transfected with potential tumour associated antigens. Here we
provide a computational pipeline to find the minimal set of epitopes based on patient
haplotypes and patient specific mutation profile that help in simulating cytotoxic
T cell mediated immunity.
Method
We identified over expressed proteins and proteins with validated melanoma associated
mutations to predict novel tumour associated antigens. For our analysis, we considered
MHC class-1 HLA allele frequency data from the German population eight (www.allelefrequencies.net). For epitopes with known mutations in melanoma, we generated 3D structures and performed
molecular docking and molecular dynamics simulation analysis to understand the impact
of mutation on their binding affinity with HLA alleles and T-cell receptor.
Finding
Using our computational analysis, we identified unique epitopes from proteins MCSP,
MAGE-A3, Melan-A and survivin overexpressed in melanoma. We also used BRAF, NRAS,
RAC1, KIT, STK19, MAP2K1 and CTNNB1 proteins with known mutations in case of melanoma.
Discussion
Our computational workflow is able to identify novel epitope sets with high confidence
for experimental validations.
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