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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy. / Dolton, Garry; Rius, Cristina; Wall, Aaron; Szomolay, Barbara; Bianchi, Valentina; Galloway, Sarah A.E.; Hasan, Md Samiul; Morin, Théo; Caillaud, Marine E.; Thomas, Hannah L.; Theaker, Sarah; Tan, Li Rong; Fuller, Anna; Topley, Katie; Legut, Mateusz; Attaf, Meriem; Hopkins, Jade R.; Behiry, Enas; Zabkiewicz, Joanna; Alvares, Caroline; Lloyd, Angharad; Rogers, Amber; Henley, Peter; Fegan, Christopher; Ottmann, Oliver; Man, Stephen; Crowther, Michael D.; Donia, Marco; Svane, Inge Marie; Cole, David K.; Brown, Paul E.; Rizkallah, Pierre; Sewell, Andrew K.

In: Cell, Vol. 186, No. 16, 2023, p. 3333-3349.e27.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

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, vol. 186, no. 16, pp. 3333-3349.e27. https://doi.org/10.1016/j.cell.2023.06.020

APA

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

Vancouver

Dolton G, Rius C, Wall A, Szomolay B, Bianchi V, Galloway SAE et al. Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy. Cell. 2023;186(16):3333-3349.e27. https://doi.org/10.1016/j.cell.2023.06.020

Author

Dolton, Garry ; Rius, Cristina ; Wall, Aaron ; Szomolay, Barbara ; Bianchi, Valentina ; Galloway, Sarah A.E. ; Hasan, Md Samiul ; Morin, Théo ; Caillaud, Marine E. ; Thomas, Hannah L. ; Theaker, Sarah ; Tan, Li Rong ; Fuller, Anna ; Topley, Katie ; Legut, Mateusz ; Attaf, Meriem ; Hopkins, Jade R. ; Behiry, Enas ; Zabkiewicz, Joanna ; Alvares, Caroline ; Lloyd, Angharad ; Rogers, Amber ; Henley, Peter ; Fegan, Christopher ; Ottmann, Oliver ; Man, Stephen ; Crowther, Michael D. ; Donia, Marco ; Svane, Inge Marie ; Cole, David K. ; Brown, Paul E. ; Rizkallah, Pierre ; Sewell, Andrew K. / Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy. In: Cell. 2023 ; Vol. 186, No. 16. pp. 3333-3349.e27.

Bibtex

@article{cd2c25110b5744138920a3836115d7db,

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 = "cancer immunotherapy, HLA class I, peptide-HLA, T cell receptor, TCR, TCR-T, TIL therapy, TILs, tumor-infiltrating lymphocytes",

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.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

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

language = "English",

volume = "186",

pages = "3333--3349.e27",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "16",

}

RIS

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

Y1 - 2023

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 - cancer immunotherapy

KW - HLA class I

KW - peptide-HLA

KW - T cell receptor

KW - TCR

KW - TCR-T

KW - TIL therapy

KW - TILs

KW - tumor-infiltrating lymphocytes

U2 - 10.1016/j.cell.2023.06.020

DO - 10.1016/j.cell.2023.06.020

M3 - Journal article

C2 - 37490916

AN - SCOPUS:85166627104

VL - 186

SP - 3333-3349.e27

JO - Cell

JF - Cell

SN - 0092-8674

IS - 16

ER -

ID: 370796382

Department of Clinical Medicine