Science

James Crowley: The identification of tumor-specific targets in expanding immunotherapy development

exponent.com

Feb 3, 2025, 11:59

James Crowley: The identification of tumor-specific targets in expanding immunotherapy development

James Crowley, Professor of Medicine Emeritus at Brown University, shared a post on LinkedIn by John Gordon, Professor Emeritus at the University of Birmingham, about a recent paper by Mark Yarmarkovich et al. published in bioRxiv:

“A pan-cancer atlas of T cell targets”

Authors: Mark Yarmarkovich et al.

“Applying this pipeline to >1,500 immunopeptidomics datasets, we identified thousands of tumor-specific targets across 21 cancer types, stemming from 11 different classes of molecular events.

This work addresses the first critical step in expanding immunotherapy development: the identification of tumor-specific targets.”

Quoting John Gordon’s post:

“In Case Anyone has Missed this phenomenal Study / Resource posted last week: ‘A pan-Cancer Atlas of T cell Targets’ open access at BioRxiv.

From lead author, Mark Yarmarkovich, PhD: ‘I’m pleased to share the first preprint from our lab describing a pan-cancer atlas of therapeutic T cell targets. Our exceptional bioinformatics postdoc, Guangyuan Li (Frank), executed this tour-de-force, developing a pipeline for comprehensively characterizing T cell targets. This approach integrates RNA-seq, immunopeptidomics, and single-cell sequencing.

Applying this pipeline to >1,500 immunopeptidomics datasets, we identified thousands of tumor-specific targets across 21 cancer types, stemming from 11 different classes of molecular events.

While T cell therapies are curative in several cancer settings, their applications have been limited to a subset of tumor types, leaving most patients without viable options within this powerful class of therapies. This work addresses the first critical step in expanding immunotherapy development: the identification of tumor-specific targets.

We describe numerous tumor-specific targets across cancer types including self-antigens, tumor-specific splicing variants, pathogen-derived peptides, and a number of targets derived from the ‘dark matter’ of the genome. These discoveries offer exciting potential for developing CARs, PC-CARs, TCRs, TILS, and more.

We will be releasing this resource as an interactive web portal for the scientific community and hope this will catalyze the development of safe and effective new T cell therapies’.

Overview of the Analytical Pipeline and Immunopeptidome Atlas

Illustrations of the cancer types included in this study, cancer abbreviation and full name are provided in method section |
Computational pipeline detailing the steps used to identify, refine, and enhance the detection of tumor-specific antigens, along with a depiction of the functionalities of associated interactive web portal.”

James Crowley: The identification of tumor-specific targets in expanding immunotherapy development