Identification of tumor antigens in the HLA peptidome of patient-derived xenograft tumors in mouse

Nataly Mancette Rijensky, Netta R. Blondheim Shraga, Eilon Barnea, Nir Peled, Eli Rosenbaum, Aron Popovtzer, Solomon M. Stemmer, Alejandro Livoff, Mark Shlapobersky, Neta Moskovits, Dafna Perry, Eitan Rubin, Itzhak Haviv, Arie Admon

Research output: Contribution to journalArticlepeer-review

Abstract

Personalized cancer immunotherapy targeting patient-specific cancer/testis antigens (CTA) and neoantigens may benefit from large-scale tumor human leukocyte antigen (HLA) peptidome (immunopeptidome) analysis, which aims to accurately identify antigens presented by tumor cells. While significant efforts have been invested in analyzing the HLA peptidomes of fresh tumors, it is often impossible to obtain sufficient volumes of tumor tissues for comprehensive HLA peptidome characterization. This work attempted to overcome some of these obstacles by using patient-derived xenograft tumors (PDX) in mice as the tissue sources for HLA peptidome analysis. PDX tumors provide a proxy for the expansion of the patient tumor by re-grafting them through several passages to immune-compromised mice. The HLA peptidomes of human biopsies were compared to those derived from PDX tumors. Larger HLA peptidomes were obtained from the significantly larger PDX tumors as compared to the patient biopsies. The HLA peptidomes of different PDX tumors derived from the same source tumor biopsy were very reproducible, even following subsequent passages to new naïve mice. A large number of CTA-derived HLA peptides were discovered, as well as several potential neoantigens/variant sequences. Taken together, the use of PDX tumors for HLA peptidome analysis serves as a highly expandable and stable source of reproducible and authentic peptidomes, opening up new opportunities for defining large HLA peptidomes when only small tumor biopsies are available. This approach provides a large source for tumor antigens identification, potentially useful for personalized immunotherapy.

Original languageEnglish
Pages (from-to)1360-1374
Number of pages15
JournalMolecular and Cellular Proteomics
Volume19
Issue number8
DOIs
StatePublished - Aug 2020

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