Target isoforms are an overlooked challenge and opportunity in chimeric antigen receptor cell therapy

Mike Bogetofte Barnkob; Kristoffer Vitting-Seerup; Lars Rønn Olsen

doi:10.1093/immadv/ltac009

Target isoforms are an overlooked challenge and opportunity in chimeric antigen receptor cell therapy

Immunother Adv. 2022 Apr 20;2(1):ltac009. doi: 10.1093/immadv/ltac009. eCollection 2022.

Authors

Mike Bogetofte Barnkob¹, Kristoffer Vitting-Seerup², Lars Rønn Olsen²

Affiliations

¹ Centre for Cellular Immunotherapy of Haematological Cancer Odense (CITCO), Department of Clinical Immunology, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
² Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.

Abstract

The development of novel chimeric antigen receptor (CAR) cell therapies is rapidly growing, with 299 new agents being reported and 109 new clinical trials initiated so far this year. One critical lesson from approved CD19-specific CAR therapies is that target isoform switching has been shown to cause tumour relapse, but little is known about the isoforms of CAR targets in solid cancers. Here we assess the protein isoform landscape and identify both the challenges and opportunities protein isoform switching present as CAR therapy is applied to solid cancers.

Keywords: Chimeric antigen receptor therapy; cancer; epitopes; isoform switching.