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靶向卵巢癌中TAG-72和CD47的工程化嵌合抗原受体T细胞。

Engineered CAR-T cells targeting TAG-72 and CD47 in ovarian cancer.

作者信息

Shu Runzhe, Evtimov Vera J, Hammett Maree V, Nguyen Nhu-Y N, Zhuang Junli, Hudson Peter J, Howard Maureen C, Pupovac Aleta, Trounson Alan O, Boyd Richard L

机构信息

Cartherics Pty, Ltd., Clayton, VIC 3168, Australia.

Avipep Pty, Ltd., Parkville, VIC 3052, Australia.

出版信息

Mol Ther Oncolytics. 2021 Jan 16;20:325-341. doi: 10.1016/j.omto.2021.01.002. eCollection 2021 Mar 26.


DOI:10.1016/j.omto.2021.01.002
PMID:33614914
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7868933/
Abstract

Chimeric antigen receptor (CAR) T cells have revolutionized blood cancer immunotherapy; however, their efficacy against solid tumors has been limited. A common mechanism of tumor escape from single target therapies is downregulation or mutational loss of the nominal epitope. Targeting multiple antigens may thus improve the effectiveness of CAR immunotherapies. We generated dual CAR-T cells targeting two tumor antigens: TAG-72 (tumor-associated glycoprotein 72) and CD47. TAG-72 is a pan-adenocarcinoma oncofetal antigen, highly expressed in ovarian cancers, with increased expression linked to disease progression. CD47 is ubiquitously overexpressed in multiple tumor types, including ovarian cancer; it is a macrophage "don't eat me" signal. However, CD47 is also expressed on many normal cells. To avoid this component of the dual CAR-T cells killing healthy tissue, we designed a truncated CD47 CAR devoid of intracellular signaling domains. The CD47 CAR facilitates binding to CD47 cells, increasing the prospect of TAG-72 cell elimination via the TAG-72 CAR. Furthermore, we could reduce the damage to normal tissue by monomerizing the CD47 CAR. Our results indicate that the co-expression of the TAG-72 CAR and the CD47-truncated monomer CAR on T cells could be an effective, dual CAR-T cell strategy for ovarian cancer, also applicable to other adenocarcinomas.

摘要

嵌合抗原受体(CAR)T细胞彻底改变了血癌免疫疗法;然而,它们对实体瘤的疗效一直有限。肿瘤从单一靶点疗法中逃逸的常见机制是名义表位的下调或突变缺失。因此,靶向多种抗原可能会提高CAR免疫疗法的有效性。我们生成了靶向两种肿瘤抗原的双特异性CAR-T细胞:TAG-72(肿瘤相关糖蛋白72)和CD47。TAG-72是一种泛腺癌癌胚抗原,在卵巢癌中高度表达,其表达增加与疾病进展相关。CD47在包括卵巢癌在内的多种肿瘤类型中普遍过度表达;它是一种巨噬细胞“别吃我”信号。然而,CD47也在许多正常细胞上表达。为避免双特异性CAR-T细胞的这一组成部分杀死健康组织,我们设计了一种不含细胞内信号结构域的截短型CD47 CAR。CD47 CAR有助于与CD47细胞结合,增加通过TAG-72 CAR消除TAG-72细胞的可能性。此外,我们可以通过将CD47 CAR单体化来减少对正常组织的损伤。我们的结果表明,在T细胞上共表达TAG-72 CAR和截短型单体CD47 CAR可能是一种有效的卵巢癌双特异性CAR-T细胞策略,也适用于其他腺癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/0243d5797742/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/1f389a8ec647/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/d413a250b19d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/e1d70fb565a2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/082601535009/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/937b39f880c9/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/4ee3e79886b9/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/5e61c287f46b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/0243d5797742/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/1f389a8ec647/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/d413a250b19d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/e1d70fb565a2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/082601535009/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/937b39f880c9/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/4ee3e79886b9/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/5e61c287f46b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71dc/7868933/0243d5797742/gr7.jpg

相似文献

[1]
Engineered CAR-T cells targeting TAG-72 and CD47 in ovarian cancer.

Mol Ther Oncolytics. 2021-1-16

[2]
CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth.

Cancers (Basel). 2017-10-21

[3]
The application of HER2 and CD47 CAR-macrophage in ovarian cancer.

J Transl Med. 2023-9-22

[4]
CD47 expression is critical for CAR T-cell survival in vivo.

J Immunother Cancer. 2023-3

[5]
Effective Targeting of TAG72 Peritoneal Ovarian Tumors via Regional Delivery of CAR-Engineered T Cells.

Front Immunol. 2018-11-19

[6]
Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma.

Cancers (Basel). 2020-1-28

[7]
Elimination of tumor by CD47/PD-L1 dual-targeting fusion protein that engages innate and adaptive immune responses.

MAbs. 2017-12-20

[8]
Emerging immunotherapeutics in adenocarcinomas: A focus on CAR-T cells.

Curr Trends Immunol. 2016

[9]
Therapeutic effect of dual CAR-T targeting PDL1 and MUC16 antigens on ovarian cancer cells in mice.

BMC Cancer. 2020-7-20

[10]
The CD47 "don't eat me signal" is highly expressed in human ovarian cancer.

Gynecol Oncol. 2016-11

引用本文的文献

[1]
Optimal pairing of binder and co-stimulatory domains improves dual CART cell efficacy.

Mol Ther. 2025-8-5

[2]
Advances and obstacles of T cell-based immunotherapy in gynecological malignancies.

Mol Cancer. 2025-7-26

[3]
Development and Potent Anti-Tumor Activity of a Fully Humanized Anti-TAG-72-IL-2 Fusion Protein for Therapy of Solid Tumors.

Cancers (Basel). 2025-4-26

[4]
From molecular design to clinical translation: dual-targeted CAR-T strategies in cancer immunotherapy.

Int J Biol Sci. 2025-3-31

[5]
CRISPR-Cas9 knockout of DGKα/ζ improves the anti-tumor activities of TAG-72 CAR-T cells in ovarian cancer.

Mol Ther Oncol. 2025-3-5

[6]
CAR-T therapy for endocrine neoplasms: novel targets and combination of therapies.

Front Endocrinol (Lausanne). 2025-2-11

[7]
Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies.

J Hematol Oncol. 2024-11-5

[8]
Glycan diversity in ovarian cancer: Unraveling the immune interplay and therapeutic prospects.

Semin Immunopathol. 2024-10-21

[9]
Sialyl-Tn glycan epitope as a target for pancreatic cancer therapies.

Front Oncol. 2024-9-13

[10]
Targeting TAG-72 in cutaneous T cell lymphoma.

Heliyon. 2024-8-22

本文引用的文献

[1]
First clinical study of a pegylated diabody I-labeled PEG-AVP0458 in patients with tumor-associated glycoprotein 72 positive cancers.

Theranostics. 2020

[2]
The CD28 Transmembrane Domain Contains an Essential Dimerization Motif.

Front Immunol. 2020

[3]
KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma.

N Engl J Med. 2020-4-2

[4]
Parallel Comparison of 4-1BB or CD28 Co-stimulated CD19-Targeted CAR-T Cells for B Cell Non-Hodgkin's Lymphoma.

Mol Ther Oncolytics. 2019-8-28

[5]
CD47 promotes cell growth and motility in epithelial ovarian cancer.

Biomed Pharmacother. 2019-9-4

[6]
Phase I Study of Lentiviral-Transduced Chimeric Antigen Receptor-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers.

Mol Ther. 2019-7-30

[7]
Target selection of CAR T cell therapy in accordance with the TME for solid tumors.

Am J Cancer Res. 2019-2-1

[8]
First-in-Human, First-in-Class Phase I Trial of the Anti-CD47 Antibody Hu5F9-G4 in Patients With Advanced Cancers.

J Clin Oncol. 2019-2-27

[9]
CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment.

Front Immunol. 2019-2-5

[10]
Effective Targeting of TAG72 Peritoneal Ovarian Tumors via Regional Delivery of CAR-Engineered T Cells.

Front Immunol. 2018-11-19

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