Healthy cells functionally present TAP-independent SSR1 peptides: implications for selection of clinically relevant antigens
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract Tumors with an impaired transporter associated with antigen processing (TAP) present several ER-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 using a new toolbox consisting of a T cell clone recognizing a TAP-independent SSR1-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.
Authors 11
-
Sanquin · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Immunopathology, Sanquin Research, Amsterdam, 1066 CX, The Netherlands
Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, 1066 CX, The Netherlands
Department of Immunopathology, Sanquin Research, Amsterdam, 066 CX, The Netherlands
-
Sanquin · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Immunopathology, Sanquin Research, Amsterdam, 1066 CX, The Netherlands
Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, 1066 CX, The Netherlands
Department of Immunopathology, Sanquin Research, Amsterdam, 066 CX, The Netherlands
-
Sanquin · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Immunopathology, Sanquin Research, Amsterdam, 1066 CX, The Netherlands
Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, 1066 CX, The Netherlands
Department of Immunopathology, Sanquin Research, Amsterdam, 066 CX, The Netherlands
-
Leiden University Medical Center
Affiliation as printed
Department of Hematology, LUMC, Leiden, 2333 ZA, The Netherlands
Department of Hematology, LUMC, Leiden, 2 ZA, The Netherlands
-
Leiden University Medical Center · Sanquin · Oncode Institute · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Immunopathology, Sanquin Research, Amsterdam, 1066 CX, The Netherlands
Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, 1066 CX, The Netherlands
Oncode Institute and Department of Cell and Chemical Biology, LUMC, Leiden, 2333 ZA, The Netherlands
Department of Immunopathology, Sanquin Research, Amsterdam, 066 CX, The Netherlands
-
Sanquin · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Immunopathology, Sanquin Research, Amsterdam, 1066 CX, The Netherlands
Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, 1066 CX, The Netherlands
Department of Immunopathology, Sanquin Research, Amsterdam, 066 CX, The Netherlands
-
Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, LUMC, Leiden, 2333 ZA, The Netherlands
-
Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, LUMC, Leiden, 2333 ZA, The Netherlands
-
Leiden University Medical Center
Affiliation as printed
Department of Hematology, LUMC, Leiden, 2333 ZA, The Netherlands
Department of Hematology, LUMC, Leiden, 2 ZA, The Netherlands
-
Leiden University Medical Center
Affiliation as printed
Department of Hematology, LUMC, Leiden, 2333 ZA, The Netherlands
Department of Hematology, LUMC, Leiden, 2 ZA, The Netherlands
-
Robbert M. Spaapen corresponding
Sanquin · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Immunopathology, Sanquin Research, Amsterdam, 1066 CX, The Netherlands
Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, 1066 CX, The Netherlands
Department of Immunopathology, Sanquin Research, Amsterdam, 066 CX, The Netherlands
Cited by 1 stored of 1
1 result
Cited by patents worldwide 4 (Lens.org)
-
T CELL RECEPTORS DIRECTED AGAINST CANCER-ASSOCIATED ANTIGENS AND USES THEREOFNL2033510B1 2024-05-28 Active
-
T CELL RECEPTORS DIRECTED AGAINST CANCER-ASSOCIATED ANTIGENS AND USES THEREOFWO2024101994A1 2024-05-16 Pending Aachen patent
-
T CELL RECEPTORS DIRECTED AGAINST TRANSCRIPTION FACTOR WT1 AND USES THEREOFNL2031118B1 2023-09-07 Inactive Aachen patent
-
T CELL RECEPTORS DIRECTED AGAINST TRANSCRIPTION FACTOR WT1 AND USES THEREOFWO2023167583A1 2023-09-07 Pending