Journal
ISCIENCE
Volume 24, Issue 2, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2021.102051
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Funding
- Netherlands organization for scientific research (NWO-VIDI) [91719369]
- KWF Alpe d'HuZes [2015-7982]
- Landsteiner Foundation for Blood Transfusion Research (LSBR fellowship) [1842F]
- NWO Medium (ZonMw) [91116004]
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The absence of clinically relevant antigens on healthy cells needs to be extensively tested in order to define safe targets for T cell-based immunotherapy.
Tumors with an impaired transporter associated with antigen processing (TAP) present several endoplasmic reticulum-derived self-antigens on HLA class I (HLA-I) which are absent on healthy cells. Selection of such TAP-independent antigens for T cell-based immunotherapy should include analysis of their expression on healthy cells to prevent therapy-induced adverse toxicities. However, it is unknown how the absence of clinically relevant antigens on healthy cells needs to be validated. Here, we monitored TAP-independent antigen presentation on various healthy cells after establishing a T cell tool recognizing a TAP-independent signal sequence receptor 1-derived antigen. We found that most but not all healthy cells present this antigen under normal and inflammatory conditions, indicating that TAP-independent antigen presentation is a variable phenomenon. Our data emphasize the necessity of extensive testing of a wide variety of healthy cell types to define clinically relevant TAP-independent antigens that can be safely targeted by immunotherapy.
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