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嵌合抗原受体(CAR)T细胞产品中的旁观者CAR CD8⁺ T细胞可以扩增并增强双特异性抗体的抗肿瘤作用。

Bystander CARCD8 T cells in a CAR-T cell product can expand and enhance the antitumor effects of a bispecific antibody.

作者信息

Kato Junichi, Konishi Tatsuya, Honda Takatsugu, Maruta Masaki, Nabe Shogo, Masuda Yuya, Matsumoto Meika, Kawasaki Natsumi, Miyazaki Yukihiro, Doi Yasukazu, Takasuka Yasunori, Yamanouchi Jun, Ochi Toshiki, Takenaka Katsuto

机构信息

Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

Division of Blood Transfusion and Cell Therapy, Ehime University Hospital, Toon, Ehime, Japan.

出版信息

J Immunother Cancer. 2025 Jun 24;13(6):e011690. doi: 10.1136/jitc-2025-011690.


DOI:10.1136/jitc-2025-011690
PMID:40555560
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12198839/
Abstract

Although bispecific antibody (BsAb) treatment is a valuable therapeutic option for post chimeric antigen receptor (CAR)-T cell therapy against relapsed/refractory large B-cell lymphoma, it remains to be clarified why it is still effective after intensive T-cell redirection therapy. Recently, the therapeutic potential of bystander CD8 T cells in the field of cancer immunotherapy have been discussed. In this study, we have shown a clinical impact where bystander CAR-negative CD8 T cells from a CAR-T cell product have a potential to augment immune responses of BsAb therapy through a case with relapsed diffuse large B-cell lymphoma after CD19 CAR-T cell therapy. T cells in a CAR-T-cell product dominantly showed central and effector memory T cells, and such T-cell phenotypes in peripheral blood significantly increased after CAR-T cell therapy. Furthermore, chronological T-cell receptor-β repertoire analyses for both CD8 T cells and CD4 T cells suggested that product-derived bystander CARCD8 T cells successfully existed in a relapsed lymph node and expanded in the body after BsAb therapy. Further analyses are necessary, but our findings might help to explain the mechanisms and benefits of this sequential approach and strengthen the sequence of CAR-T cell therapy prior to BsAb therapy.

摘要

尽管双特异性抗体(BsAb)治疗是嵌合抗原受体(CAR)-T细胞疗法治疗复发/难治性大B细胞淋巴瘤后的一种有价值的治疗选择,但在强化T细胞重定向治疗后其仍有效的原因尚待阐明。最近,癌症免疫治疗领域中旁观者CD8 T细胞的治疗潜力已被讨论。在本研究中,我们通过一例CD19 CAR-T细胞治疗后复发的弥漫性大B细胞淋巴瘤病例,展示了CAR-T细胞产品中旁观者CAR阴性CD8 T细胞有可能通过增强BsAb治疗的免疫反应而产生临床影响。CAR-T细胞产品中的T细胞主要表现为中枢和效应记忆T细胞,且CAR-T细胞治疗后外周血中此类T细胞表型显著增加。此外,对CD8 T细胞和CD4 T细胞进行的时间顺序T细胞受体-β谱系分析表明,产品来源的旁观者CAR CD8 T细胞在复发淋巴结中成功存在,并在BsAb治疗后在体内扩增。虽然还需要进一步分析,但我们的发现可能有助于解释这种序贯治疗方法的机制和益处,并加强CAR-T细胞治疗先于BsAb治疗的顺序。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee6/12198839/e032421262cc/jitc-13-6-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee6/12198839/2acf34365789/jitc-13-6-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee6/12198839/e032421262cc/jitc-13-6-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee6/12198839/2acf34365789/jitc-13-6-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee6/12198839/e032421262cc/jitc-13-6-g002.jpg

相似文献

[1]
Bystander CARCD8 T cells in a CAR-T cell product can expand and enhance the antitumor effects of a bispecific antibody.

J Immunother Cancer. 2025-6-24

[2]
Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma.

Cochrane Database Syst Rev. 2021-9-13

[3]
Revaccination following CAR-T therapy: a needs assessment.

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[4]
Enrichment of CD7CXCR3 CAR T-cells in infusion products is associated with durable remission in relapsed or refractory diffuse large B-cell lymphoma.

Ann Oncol. 2025-7

[5]
The Role of Radiotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Post-CAR-T Therapy: A Systematic Literature Review.

Technol Cancer Res Treat. 2025

[6]
[Modern systemic treatment-bispecific antibodies and CAR-T cell therapy : Clinical management, mechanisms of action, outcomes].

Radiologie (Heidelb). 2025-6-13

[7]
Membrane-bound IL-7 immobilized by the CD8 transmembrane region improves efficacy of CD19 CAR-T cell therapy.

Mol Cancer. 2024-10-23

[8]
5-5-5 ABRT (Dose of 5 Gy per Fraction for up to 5 Fractions Over 5 Weeks Adaptive Bridging Radiation Therapy)-Artificial Intelligence Enters the CAR (-T) (Chimeric Antigen Receptor-T) in Relapsed/Refractory Large B Cell Lymphoma.

Int J Radiat Oncol Biol Phys. 2025-7-15

[9]
Immunological consequences of CAR T-cell therapy: an analysis of infectious complications and immune reconstitution.

Blood Adv. 2025-7-8

[10]
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Front Immunol. 2025-6-6

本文引用的文献

[1]
Bispecific CAR-T cells targeting CD19/20 in patients with relapsed or refractory B cell non-Hodgkin lymphoma: a phase I/II trial.

Blood Cancer J. 2024-8-7

[2]
CD20-bispecific antibodies improve response to CD19-CAR T cells in lymphoma in vitro and CLL in vivo models.

Blood. 2024-8-15

[3]
IL-7-primed bystander CD8 tumor-infiltrating lymphocytes optimize the antitumor efficacy of T cell engager immunotherapy.

Cell Rep Med. 2024-5-21

[4]
B-cell-directed CAR T-cell therapy activates CD8+ cytotoxic CARneg bystander T cells in patients and nonhuman primates.

Blood. 2024-7-4

[5]
CAR-T cell manufacturing: Major process parameters and next-generation strategies.

J Exp Med. 2024-2-5

[6]
Lymphodepletion - an essential but undervalued part of the chimeric antigen receptor T-cell therapy cycle.

Front Immunol. 2023

[7]
Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma.

Blood Adv. 2023-9-12

[8]
Long-term outcomes following CAR T cell therapy: what we know so far.

Nat Rev Clin Oncol. 2023-6

[9]
Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial.

J Clin Oncol. 2023-4-20

[10]
Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

N Engl J Med. 2022-12-15

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