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Rejection resistant CD30.CAR-modified Epstein-Barr virus-specific T cells as an off-the-shelf platform for CD30 lymphoma.

作者信息

Quach David H, Ganesh Haran R, Briones Yolanda D, Nouraee Nazila, Ma Audrey, Hadidi Yezan F, Sharma Sandhya, Rooney Cliona M

机构信息

Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, and Houston Methodist Hospital, Houston, TX 77030, USA.

Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

出版信息

Mol Ther Oncol. 2024 May 14;32(2):200814. doi: 10.1016/j.omton.2024.200814. eCollection 2024 Jun 20.


DOI:10.1016/j.omton.2024.200814
PMID:38966037
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11223124/
Abstract

Off-the-shelf (OTS) adoptive T cell therapies have many benefits such as immediate availability, improved access and reduced cost, but face the major challenges of graft-vs-host disease (GVHD) and graft rejection, mediated by alloreactive T cells present in the graft and host, respectively. We have developed a platform for OTS T cell therapies by using Epstein-Bar virus (EBV)-specific T cells (EBVSTs) expressing a chimeric antigen receptor (CAR) targeting CD30. Allogeneic EBVSTs have not caused GVHD in several clinical trials, while the CD30.CAR, that is effective for the treatment of lymphoma, can also target alloreactive T cells that upregulate CD30 on activation. Although EBVSTs express high levels of CD30, they were protected from fratricide , by the CD30.CAR. Hence, they could proliferate extensively and maintained function both through their native EBV-specific T cell receptor and the CD30.CAR. The CD30.CAR enabled EBVSTs to persist in co-cultures with naive and primed alloreactive T cells and eliminate activated natural killer cells that can also be alloreactive. In conclusion, we show that CD30.CAR EBVSTs have the potential to be an effective OTS therapy against CD30 tumors and, if successful, could then be used as a platform to target other tumor antigens.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/366c6e0c7f82/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/623122d1827d/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/4ae9e6818e03/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/45d9f326ce60/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/bedb1d6faac1/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/b63fb1958e6b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/c2e89384c2f5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/81f1d96626e7/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/366c6e0c7f82/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/623122d1827d/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/4ae9e6818e03/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/45d9f326ce60/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/bedb1d6faac1/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/b63fb1958e6b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/c2e89384c2f5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/81f1d96626e7/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e24/11223124/366c6e0c7f82/gr7.jpg

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本文引用的文献

[1]
Naive T cells inhibit the outgrowth of intractable antigen-activated memory T cells: implications for T-cell immunotherapy.

J Immunother Cancer. 2023-4

[2]
Third-party CMV- and EBV-specific T-cells for first viral reactivation after allogeneic stem cell transplant.

Blood Adv. 2022-9-13

[3]
Endowing universal CAR T-cell with immune-evasive properties using TALEN-gene editing.

Nat Commun. 2022-6-30

[4]
Understanding natural killer cell biology from a single cell perspective.

Cell Immunol. 2022-3

[5]
Functional virus-specific memory T cells survey glioblastoma.

Cancer Immunol Immunother. 2022-8

[6]
Mutant B2M-HLA-E and B2M-HLA-G fusion proteins protects universal chimeric antigen receptor-modified T cells from allogeneic NK cell-mediated lysis.

Eur J Immunol. 2021-10

[7]
Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma.

J Clin Oncol. 2020-11-10

[8]
Engineered off-the-shelf therapeutic T cells resist host immune rejection.

Nat Biotechnol. 2021-1

[9]
Genetic Ablation of HLA Class I, Class II, and the T-cell Receptor Enables Allogeneic T Cells to Be Used for Adoptive T-cell Therapy.

Cancer Immunol Res. 2020-7

[10]
Expanding CAR T cells in human platelet lysate renders T cells with in vivo longevity.

J Immunother Cancer. 2019-11-28

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