Research ExplorerPublicationsPotent suppression of neuroendocrine tumors and gastrointest...

Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues

Standard

Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues. / Feng, Zijie; He, Xin; Zhang, Xuyao; Wu, Yuan; Xing, Bowen; Knowles, Alison; Shan, Qiaonan; Miller, Samuel; Hojnacki, Taylor; Ma, Jian; Katona, Bryson W; Gade, Terence P F; Schrader, Jörg; Metz, David C; June, Carl H; Hua, Xianxin.

In: NAT CANCER, Vol. 3, No. 5, 05.2022, p. 581-594.

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

Harvard

Feng, Z, He, X, Zhang, X, Wu, Y, Xing, B, Knowles, A, Shan, Q, Miller, S, Hojnacki, T, Ma, J, Katona, BW, Gade, TPF, Schrader, J, Metz, DC, June, CH & Hua, X 2022, 'Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues', NAT CANCER, vol. 3, no. 5, pp. 581-594. https://doi.org/10.1038/s43018-022-00344-7

APA

Feng, Z., He, X., Zhang, X., Wu, Y., Xing, B., Knowles, A., Shan, Q., Miller, S., Hojnacki, T., Ma, J., Katona, B. W., Gade, T. P. F., Schrader, J., Metz, D. C., June, C. H., & Hua, X. (2022). Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues. NAT CANCER, 3(5), 581-594. https://doi.org/10.1038/s43018-022-00344-7

Vancouver

Feng Z, He X, Zhang X, Wu Y, Xing B, Knowles A et al. Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues. NAT CANCER. 2022 May;3(5):581-594. https://doi.org/10.1038/s43018-022-00344-7

Bibtex

@article{6abcb1e3f8614b248e9df6e3e116cc0b,
title = "Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues",
abstract = "Gastrointestinal cancers (GICs) and neuroendocrine tumors (NETs) are often refractory to therapy after metastasis. Adoptive cell therapy using chimeric antigen receptor (CAR) T cells, though remarkably efficacious for treating leukemia, is yet to be developed for solid tumors such as GICs and NETs. Here we isolated a llama-derived nanobody, VHH1, and found that it bound cell surface adhesion protein CDH17 upregulated in GICs and NETs. VHH1-CAR T cells (CDH17CARTs) killed both human and mouse tumor cells in a CDH17-dependent manner. CDH17CARTs eradicated CDH17-expressing NETs and gastric, pancreatic and colorectal cancers in either tumor xenograft or autochthonous mouse models. Notably, CDH17CARTs do not attack normal intestinal epithelial cells, which also express CDH17, to cause toxicity, likely because CDH17 is localized only at the tight junction between normal intestinal epithelial cells. Thus, CDH17 represents a class of previously unappreciated tumor-associated antigens that is 'masked' in healthy tissues from attack by CAR T cells for developing safer cancer immunotherapy.",
author = "Zijie Feng and Xin He and Xuyao Zhang and Yuan Wu and Bowen Xing and Alison Knowles and Qiaonan Shan and Samuel Miller and Taylor Hojnacki and Jian Ma and Katona, {Bryson W} and Gade, {Terence P F} and J{\"o}rg Schrader and Metz, {David C} and June, {Carl H} and Xianxin Hua",
note = "{\textcopyright} 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = may,
doi = "10.1038/s43018-022-00344-7",
language = "English",
volume = "3",
pages = "581--594",
journal = "NAT CANCER",
issn = "2662-1347",
publisher = "NATURE PUBLISHING GROUP",
number = "5",

}

RIS

TY - JOUR

T1 - Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues

AU - Feng, Zijie

AU - He, Xin

AU - Zhang, Xuyao

AU - Wu, Yuan

AU - Xing, Bowen

AU - Knowles, Alison

AU - Shan, Qiaonan

AU - Miller, Samuel

AU - Hojnacki, Taylor

AU - Ma, Jian

AU - Katona, Bryson W

AU - Gade, Terence P F

AU - Schrader, Jörg

AU - Metz, David C

AU - June, Carl H

AU - Hua, Xianxin

N1 - © 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

PY - 2022/5

Y1 - 2022/5

N2 - Gastrointestinal cancers (GICs) and neuroendocrine tumors (NETs) are often refractory to therapy after metastasis. Adoptive cell therapy using chimeric antigen receptor (CAR) T cells, though remarkably efficacious for treating leukemia, is yet to be developed for solid tumors such as GICs and NETs. Here we isolated a llama-derived nanobody, VHH1, and found that it bound cell surface adhesion protein CDH17 upregulated in GICs and NETs. VHH1-CAR T cells (CDH17CARTs) killed both human and mouse tumor cells in a CDH17-dependent manner. CDH17CARTs eradicated CDH17-expressing NETs and gastric, pancreatic and colorectal cancers in either tumor xenograft or autochthonous mouse models. Notably, CDH17CARTs do not attack normal intestinal epithelial cells, which also express CDH17, to cause toxicity, likely because CDH17 is localized only at the tight junction between normal intestinal epithelial cells. Thus, CDH17 represents a class of previously unappreciated tumor-associated antigens that is 'masked' in healthy tissues from attack by CAR T cells for developing safer cancer immunotherapy.

AB - Gastrointestinal cancers (GICs) and neuroendocrine tumors (NETs) are often refractory to therapy after metastasis. Adoptive cell therapy using chimeric antigen receptor (CAR) T cells, though remarkably efficacious for treating leukemia, is yet to be developed for solid tumors such as GICs and NETs. Here we isolated a llama-derived nanobody, VHH1, and found that it bound cell surface adhesion protein CDH17 upregulated in GICs and NETs. VHH1-CAR T cells (CDH17CARTs) killed both human and mouse tumor cells in a CDH17-dependent manner. CDH17CARTs eradicated CDH17-expressing NETs and gastric, pancreatic and colorectal cancers in either tumor xenograft or autochthonous mouse models. Notably, CDH17CARTs do not attack normal intestinal epithelial cells, which also express CDH17, to cause toxicity, likely because CDH17 is localized only at the tight junction between normal intestinal epithelial cells. Thus, CDH17 represents a class of previously unappreciated tumor-associated antigens that is 'masked' in healthy tissues from attack by CAR T cells for developing safer cancer immunotherapy.

U2 - 10.1038/s43018-022-00344-7

DO - 10.1038/s43018-022-00344-7

M3 - SCORING: Journal article

C2 - 35314826

VL - 3

SP - 581

EP - 594

JO - NAT CANCER

JF - NAT CANCER

SN - 2662-1347

IS - 5

ER -