Identification and in vitro validation of neoantigens for immune activation against high-risk pediatric leukemia cells

Hum Vaccin Immunother. 2021 Dec 2;17(12):5558-5562. doi: 10.1080/21645515.2021.2001243. Epub 2021 Nov 29.

Abstract

There is experimental and clinical data to indicate the contribution of immune-escape mechanisms in relapsed/refractory pediatric leukemia. Studies have shown the accumulation of mutations that translate to peptides containing tumor-specific epitopes (neoantigens). The effectiveness of neoantigen-based vaccines has been shown in several clinical trials in adults. Though the initial results are encouraging, this knowledge must be developed to account for the uniqueness of pediatric cancer biology. We have completed the initial proof-of-concept analysis on a high-risk pediatric leukemia specimen and identified usable neoantigen sequences. We describe this approach, including the bioinformatics method and experimental model to verify their function that can be further broadened for personalized neoantigen prediction and testing for the generation of anticancer vaccines against high-risk pediatric leukemias.

Keywords: Pediatric leukemia; cancer vaccine; high risk T-ALL; neoantigen peptide; pediatric immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Neoplasm
  • Cancer Vaccines*
  • Child
  • Humans
  • Immunotherapy / methods
  • Leukemia* / therapy
  • Neoplasms*

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines

Grants and funding

This study was supported in part by the Alberta Children’s Hospital Foundation (ACHF), Kids Cancer Care Foundation of Alberta (KCC) and the Pediatric Oncology Experimental Therapeutics Investigators’ Consortium (POETIC).