Dataset Information

Phage display enables machine learning discovery of cancer antigen specific TCRs

ABSTRACT: T cells targeting epitopes in infectious diseases or cancer play a central role in spontaneous and therapy-induced immune responses. T-cell epitope recognition is mediated by the binding of the T-Cell Receptor (TCR) and TCRs recognizing clinically relevant epitopes are promising for T-cell based therapies. Starting from one of the few known TCRs targeting the cancer-testis antigen NY-ESO-1 (157–165) epitope, we built large phage display libraries of TCRs with randomized Complementary Determining Region 3 of the β chain. The TCR libraries were panned against the NY-ESO-1 epitope, which enabled us to collect thousands of epitope-specific TCR sequences. We then trained a machine learning TCR-epitope interaction predictor with this data and could identify several epitope-specific TCRs directly from TCR repertoires. Cellular binding and functional assays revealed that the predicted TCRs displayed activity towards the NY-ESO-1 epitope and no detectable cross-reactivity with self-peptides. Overall, our work demonstrates how display technologies combined with machine learning models of TCR-epitope recognition can effectively leverage large TCR repertoires for TCR discovery.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Michal Bassani-Sternberg

LAB HEAD: Michal Bassani-Sternberg

PROVIDER: PXD058478 | Pride | 2025-06-20

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20241111_DIA_COL059-00001-HLAIp_R03.raw	Raw
	20241111_DIA_COL059-00001-HLAIp_R04.raw	Raw
	20241111_DIA_COL059-00002-HLAIp_R03.raw	Raw
	20241111_DIA_COL059-00002-HLAIp_R04.raw	Raw
	20241111_DIA_COL059-00003-HLAIp_R03.raw	Raw

Items per page:

1 - 5 of 14

Publications

Phage display enables machine learning discovery of cancer antigen-specific TCRs.

Croce Giancarlo G Lani Rachid R Tardivon Delphine D Bobisse Sara S de Tiani Mariastella M Bragina Maiia M Perez Marta A S MAS Michaux Justine J Pak Hui Song HS Michel Alexandra A Gehret Talita T Schmidt Julien J Guillame Philippe P Bassani-Sternberg Michal M Zoete Vincent V Harari Alexandre A Rufer Nathalie N Hebeisen Michael M Dunn Steven M SM Gfeller David D

Science advances 20250611 24

T cells targeting epitopes in infectious diseases or cancer play a central role in spontaneous and therapy-induced immune responses. Epitope recognition is mediated by the binding of the T cell receptor (TCR), and TCRs recognizing clinically relevant epitopes are promising for T cell-based therapies. Starting from a TCR targeting the cancer-testis antigen NY-ESO-1<sub>157-165</sub> epitope, we built large phage display libraries of TCRs with randomized complementary determining region 3 of the β ...[more]

PMID: 40498839

Similar Datasets

Project description:Background Clinical success of T cell receptor (TCR) gene therapy has previously been demonstrated for NY-ESO-1 TCR gene therapy. To increase numbers of cancer patients that can be treated with TCR gene therapy we aimed to identify a novel set of high-affinity cancer specific TCRs targeting different cancer testis (CT) antigens in prevalent HLA class I alleles. Methods In this study, we selected based on publicly available gene expression databases the most promising CT genes to target. From these selected genes we identified by HLA peptidomics the naturally processed and presented HLA class I peptides. With these peptide-HLA tetramers were generated, and by single cell sorting CT specific CD8+ T cells were selected, and expanded from the allo-HLA repertoire of healthy donors. By several functional assays high avidity CT-specific T cell clones with safe recognition pattern were selected. To evaluate the potential for clinical application in TCR gene therapy, TCRs were sequenced and transferred into peripheral blood derived CD8+ T cells. Results In total we identified, 7 novel CT-specific TCRs that effectively target MAGE-A1, MAGE-A3, MAGE-A6 and MAGE-A9 in the context of human leukocyte antigen(HLA) -A1, -A2, -A3, -B7, -B35 and -C7. TCR gene transfer into CD8⁺ T cells resulted in efficient cytokine production and cytotoxicity of variety of different tumor types without detectable cross-reactivity. In addition, major in vivo antitumor effects of MAGE-A1 specific TCR engineered CD8⁺ T cells was observed in an orthotopic xenograft model for established multiple myeloma, in which bone marrow located tumor cells were completely eradicated after T cell injection. Conclusion The identification of 7 novel CT-specific TCRs, reactive against CT antigens presented in a variety of different HLA class I alleles, allows selection of therapeutic TCRs for an increased number of cancer patients, and will improve development of personalized TCR gene therapy.