Frontiers in Biology

, Volume 11, Issue 5, pp 366–375

Finding neoepitopes in mouse models of personalized cancer immunotherapy

  • Sahar Al Seesi
  • Alok Das Mohapatra
  • Arpita Pawashe
  • Ion I. Mandoiu
  • Fei Duan
Review

DOI: 10.1007/s11515-016-1422-2

Cite this article as:
Al Seesi, S., Das Mohapatra, A., Pawashe, A. et al. Front. Biol. (2016) 11: 366. doi:10.1007/s11515-016-1422-2
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Abstract

Background

Cancer immunotherapy uses one’s own immune system to fight cancerous cells. As immune system is hard-wired to distinguish self and non-self, cancer immunotherapy is predicted to target cancerous cells specifically, therefore is less toxic than chemotherapy and radiation therapy, two major treatments for cancer. Cancer immunologists have spent decades to search for the specific targets in cancerous cells.

Methods

Due to the recent advances in high throughput sequencing and bioinformatics, evidence has merged that the neoantigens in cancerous cells are probably the cancer-specific targets that lead to the destruction of cancer.We will review the transplantable murine tumor models for cancer immunotherapy and the bioinformatics tools used to navigate mouse genome to identify tumor-rejecting neoantigens.

Results

Several groups have independently identified point mutations that can be recognized by T cells of host immune system. It is consistent with the note that the formation of peptide-MHC I-TCR complex is critical to activate T cells. Both anchor residue and TCR-facing residue mutations have been reported. While TCR-facing residue mutations may directly activate specific T cells, anchor residue mutations improve the binding of peptides to MHC I molecules, which increases the presentation of peptides and the T cell activation indirectly.

Conclusions

Our work indicates that the affinity of neoepitopes for MHC I is not a predictor for anti-tumor immune responses in mice. Instead differential agretopic index (DAI), the numerical difference of epitope-MHC I affinities between the mutated and un-mutated sequences is a significant predictor. A similar bioinformatics pipeline has been developed to generate personalized vaccines to treat human ovarian cancer in a Phase I clinical trial.

Keywords

cancer immunotherapy tumor antigens neoantigens neoepitopes differential agretopic index (DAI) RNA-Seq single nucleotide variant (SNV) 

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Sahar Al Seesi
    • 1
    • 2
  • Alok Das Mohapatra
    • 1
  • Arpita Pawashe
    • 1
  • Ion I. Mandoiu
    • 2
  • Fei Duan
    • 1
  1. 1.Department of Immunology and Carole and Ray Neag Comprehensive Cancer CenterUniversity of Connecticut Cancer CenterFarmingtonUSA
  2. 2.Department of Computer Science & EngineeringUniversity of ConnecticutStorrsUSA

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