Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

The quest for the perfect tumor specific antigen - characterizing the oncogenic MHC ligandomes for novel therapeutic targets (#655)

Jennie R Lill 1
  1. Genentech, SOUTH SAN FRANCISCO, CALIFORNIA, United States

 

Background

Cancer Immunology is a rapidly evolving and exciting field with many new strategies for harnessing the immune system to eliminate tumors on the horizon. We have previously reported proteomic studies on the characterization and targeting of neo-antigens, leading to the development of a therapeutic approach for generating cancer vaccines. These vaccines are already showing promise in the clinic. Our current strategy expands on this, and explores novel mechanisms to find additional classes of tumor specific antigens for targeting using a combination of transcriptomics, proteomics and proteo-informatic tools.

 

Methodologies

We have employed a combination of ribosomal sequencing, MHC I proteomics and in depth proteo-informatics on a variety of primary cell lines, monoallelic engineered cells and primary tumors. We compared the effects of various cellular perturbations and small molecule inhibitors to decipher how to reveal new tumor specific antigens for potential application as biotherapeutics. Using high resolution mass spectrometry in combination with exome sequencing, ribosomal sequencing and computational strategies we reveal repertoires of peptides as targets for oncological intervention.

 

Findings

By performing various cellular perturbations and characterizing the MHC I ligandome using proteomics, we have identified several new tumor specific antigens which are currently being tested for their ability to elicit a potent immune response. If successful, these antigens will be added to our arsenal of cancer immunotherapeutic tools.