Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy

Garry Dolton; Cristina Rius; Aaron Wall; Barbara Szomolay; Valentina Bianchi; Sarah A E Galloway; Md Samiul Hasan; Théo Morin; Marine E Caillaud; Hannah L Thomas; Sarah Theaker; Li Rong Tan; Anna Fuller; Katie Topley; Mateusz Legut; Meriem Attaf; Jade R Hopkins; Enas Behiry; Joanna Zabkiewicz; Caroline Alvares; Angharad Lloyd; Amber Rogers; Peter Henley; Christopher Fegan; Oliver Ottmann; Stephen Man; Michael D Crowther; Marco Donia; Inge Marie Svane; David K Cole; Paul E Brown; Pierre Rizkallah; Andrew K Sewell

doi:10.1016/j.cell.2023.06.020

Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy

Garry Dolton, Cristina Rius, Aaron Wall, Barbara Szomolay, Valentina Bianchi, Sarah A E Galloway, Md Samiul Hasan, Théo Morin, Marine E Caillaud, Hannah L Thomas, Sarah Theaker, Li Rong Tan, Anna Fuller, Katie Topley, Mateusz Legut, Meriem Attaf, Jade R Hopkins, Enas Behiry, Joanna Zabkiewicz, Caroline AlvaresAngharad Lloyd, Amber Rogers, Peter Henley, Christopher Fegan, Oliver Ottmann, Stephen Man, Michael D Crowther, Marco Donia, Inge Marie Svane, David K Cole, Paul E Brown, Pierre Rizkallah, Andrew K Sewell

Center for Cancer Immune Therapy (CCIT), Department of Oncology, Copenhagen University Hospital , Herlev, Denmark.

68 Citationer (Scopus)

Abstract

The T cells of the immune system can target tumors and clear solid cancers following tumor-infiltrating lymphocyte (TIL) therapy. We used combinatorial peptide libraries and a proteomic database to reveal the antigen specificities of persistent cancer-specific T cell receptors (TCRs) following successful TIL therapy for stage IV malignant melanoma. Remarkably, individual TCRs could target multiple different tumor types via the HLA A∗02:01-restricted epitopes EAAGIGILTV, LLLGIGILVL, and NLSALGIFST from Melan A, BST2, and IMP2, respectively. Atomic structures of a TCR bound to all three antigens revealed the importance of the shared x-x-x-A/G-I/L-G-I-x-x-x recognition motif. Multi-epitope targeting allows individual T cells to attack cancer in several ways simultaneously. Such "multipronged" T cells exhibited superior recognition of cancer cells compared with conventional T cell recognition of individual epitopes, making them attractive candidates for the development of future immunotherapies.

Originalsprog	Engelsk
Tidsskrift	Cell
Vol/bind	186
Udgave nummer	16
Sider (fra-til)	3333-3349.e27
ISSN	0092-8674
DOI	https://doi.org/10.1016/j.cell.2023.06.020
Status	Udgivet - 3 aug. 2023

Adgang til dokumentet

10.1016/j.cell.2023.06.020

Andre filer og links

Link to publication in Scopus

Citationsformater

Dolton, G., Rius, C., Wall, A., Szomolay, B., Bianchi, V., Galloway, S. A. E., Hasan, M. S., Morin, T., Caillaud, M. E., Thomas, H. L., Theaker, S., Tan, L. R., Fuller, A., Topley, K., Legut, M., Attaf, M., Hopkins, J. R., Behiry, E., Zabkiewicz, J., ... Sewell, A. K. (2023). Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy. Cell, 186(16), 3333-3349.e27. https://doi.org/10.1016/j.cell.2023.06.020

Dolton, G, Rius, C, Wall, A, Szomolay, B, Bianchi, V, Galloway, SAE, Hasan, MS, Morin, T, Caillaud, ME, Thomas, HL, Theaker, S, Tan, LR, Fuller, A, Topley, K, Legut, M, Attaf, M, Hopkins, JR, Behiry, E, Zabkiewicz, J, Alvares, C, Lloyd, A, Rogers, A, Henley, P, Fegan, C, Ottmann, O, Man, S, Crowther, MD , Donia, M , Svane, IM, Cole, DK, Brown, PE, Rizkallah, P & Sewell, AK 2023, 'Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy', Cell, bind 186, nr. 16, s. 3333-3349.e27. https://doi.org/10.1016/j.cell.2023.06.020

@article{5f66d4372fa84045bdda5d1abd75cdbb,

title = "Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy",

abstract = "The T cells of the immune system can target tumors and clear solid cancers following tumor-infiltrating lymphocyte (TIL) therapy. We used combinatorial peptide libraries and a proteomic database to reveal the antigen specificities of persistent cancer-specific T cell receptors (TCRs) following successful TIL therapy for stage IV malignant melanoma. Remarkably, individual TCRs could target multiple different tumor types via the HLA A∗02:01-restricted epitopes EAAGIGILTV, LLLGIGILVL, and NLSALGIFST from Melan A, BST2, and IMP2, respectively. Atomic structures of a TCR bound to all three antigens revealed the importance of the shared x-x-x-A/G-I/L-G-I-x-x-x recognition motif. Multi-epitope targeting allows individual T cells to attack cancer in several ways simultaneously. Such {"}multipronged{"} T cells exhibited superior recognition of cancer cells compared with conventional T cell recognition of individual epitopes, making them attractive candidates for the development of future immunotherapies.",

keywords = "Antigens, Neoplasm/metabolism, Epitopes, Immunotherapy, Lymphocytes, Tumor-Infiltrating, Neoplasms/immunology, Proteomics, Receptors, Antigen, T-Cell/metabolism",

author = "Garry Dolton and Cristina Rius and Aaron Wall and Barbara Szomolay and Valentina Bianchi and Galloway, {Sarah A E} and Hasan, {Md Samiul} and Th{\'e}o Morin and Caillaud, {Marine E} and Thomas, {Hannah L} and Sarah Theaker and Tan, {Li Rong} and Anna Fuller and Katie Topley and Mateusz Legut and Meriem Attaf and Hopkins, {Jade R} and Enas Behiry and Joanna Zabkiewicz and Caroline Alvares and Angharad Lloyd and Amber Rogers and Peter Henley and Christopher Fegan and Oliver Ottmann and Stephen Man and Crowther, {Michael D} and Marco Donia and Svane, {Inge Marie} and Cole, {David K} and Brown, {Paul E} and Pierre Rizkallah and Sewell, {Andrew K}",

year = "2023",

month = aug,

day = "3",

doi = "10.1016/j.cell.2023.06.020",

language = "English",

volume = "186",

pages = "3333--3349.e27",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier BV",

number = "16",

}

TY - JOUR

T1 - Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy

AU - Dolton, Garry

AU - Rius, Cristina

AU - Wall, Aaron

AU - Szomolay, Barbara

AU - Bianchi, Valentina

AU - Galloway, Sarah A E

AU - Hasan, Md Samiul

AU - Morin, Théo

AU - Caillaud, Marine E

AU - Thomas, Hannah L

AU - Theaker, Sarah

AU - Tan, Li Rong

AU - Fuller, Anna

AU - Topley, Katie

AU - Legut, Mateusz

AU - Attaf, Meriem

AU - Hopkins, Jade R

AU - Behiry, Enas

AU - Zabkiewicz, Joanna

AU - Alvares, Caroline

AU - Lloyd, Angharad

AU - Rogers, Amber

AU - Henley, Peter

AU - Fegan, Christopher

AU - Ottmann, Oliver

AU - Man, Stephen

AU - Crowther, Michael D

AU - Donia, Marco

AU - Svane, Inge Marie

AU - Cole, David K

AU - Brown, Paul E

AU - Rizkallah, Pierre

AU - Sewell, Andrew K

PY - 2023/8/3

Y1 - 2023/8/3

N2 - The T cells of the immune system can target tumors and clear solid cancers following tumor-infiltrating lymphocyte (TIL) therapy. We used combinatorial peptide libraries and a proteomic database to reveal the antigen specificities of persistent cancer-specific T cell receptors (TCRs) following successful TIL therapy for stage IV malignant melanoma. Remarkably, individual TCRs could target multiple different tumor types via the HLA A∗02:01-restricted epitopes EAAGIGILTV, LLLGIGILVL, and NLSALGIFST from Melan A, BST2, and IMP2, respectively. Atomic structures of a TCR bound to all three antigens revealed the importance of the shared x-x-x-A/G-I/L-G-I-x-x-x recognition motif. Multi-epitope targeting allows individual T cells to attack cancer in several ways simultaneously. Such "multipronged" T cells exhibited superior recognition of cancer cells compared with conventional T cell recognition of individual epitopes, making them attractive candidates for the development of future immunotherapies.

AB - The T cells of the immune system can target tumors and clear solid cancers following tumor-infiltrating lymphocyte (TIL) therapy. We used combinatorial peptide libraries and a proteomic database to reveal the antigen specificities of persistent cancer-specific T cell receptors (TCRs) following successful TIL therapy for stage IV malignant melanoma. Remarkably, individual TCRs could target multiple different tumor types via the HLA A∗02:01-restricted epitopes EAAGIGILTV, LLLGIGILVL, and NLSALGIFST from Melan A, BST2, and IMP2, respectively. Atomic structures of a TCR bound to all three antigens revealed the importance of the shared x-x-x-A/G-I/L-G-I-x-x-x recognition motif. Multi-epitope targeting allows individual T cells to attack cancer in several ways simultaneously. Such "multipronged" T cells exhibited superior recognition of cancer cells compared with conventional T cell recognition of individual epitopes, making them attractive candidates for the development of future immunotherapies.

KW - Antigens, Neoplasm/metabolism

KW - Epitopes

KW - Immunotherapy

KW - Lymphocytes, Tumor-Infiltrating

KW - Neoplasms/immunology

KW - Proteomics

KW - Receptors, Antigen, T-Cell/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85166627104&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2023.06.020

DO - 10.1016/j.cell.2023.06.020

M3 - Journal article

C2 - 37490916

SN - 0092-8674

VL - 186

SP - 3333-3349.e27

JO - Cell

JF - Cell

IS - 16

ER -

Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy

Abstract

Adgang til dokumentet

Andre filer og links

Fingeraftryk

Citationsformater