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抗体修饰的 T 细胞:CARs 在血液恶性肿瘤中占据主导地位。

Antibody-modified T cells: CARs take the front seat for hematologic malignancies.

机构信息

Abramson Cancer Center.

出版信息

Blood. 2014 Apr 24;123(17):2625-35. doi: 10.1182/blood-2013-11-492231. Epub 2014 Feb 27.


DOI:10.1182/blood-2013-11-492231
PMID:24578504
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3999751/
Abstract

T cells redirected to specific antigen targets with engineered chimeric antigen receptors (CARs) are emerging as powerful therapies in hematologic malignancies. Various CAR designs, manufacturing processes, and study populations, among other variables, have been tested and reported in over 10 clinical trials. Here, we review and compare the results of the reported clinical trials and discuss the progress and key emerging factors that may play a role in effecting tumor responses. We also discuss the outlook for CAR T-cell therapies, including managing toxicities and expanding the availability of personalized cell therapy as a promising approach to all hematologic malignancies. Many questions remain in the field of CAR T cells directed to hematologic malignancies, but the encouraging response rates pave a wide road for future investigation.

摘要

嵌合抗原受体 (CAR) 修饰的靶向特定抗原的 T 细胞在血液恶性肿瘤中作为一种强大的治疗方法正在兴起。在超过 10 项临床试验中,已经测试和报告了各种 CAR 设计、制造工艺和研究人群等变量。在这里,我们回顾和比较了报告的临床试验结果,并讨论了可能对肿瘤反应产生影响的进展和关键新兴因素。我们还讨论了 CAR T 细胞疗法的前景,包括管理毒性和扩大个性化细胞疗法的可用性,作为治疗所有血液恶性肿瘤的一种有前途的方法。在针对血液恶性肿瘤的 CAR T 细胞领域仍有许多问题悬而未决,但令人鼓舞的缓解率为未来的研究铺平了道路。

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本文引用的文献

[1]
CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma.

Leukemia. 2013-9-26

[2]
Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation.

Blood. 2013-9-20

[3]
Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study.

Blood. 2013-9-12

[4]
T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia.

Blood. 2013-9-12

[5]
CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma.

Blood. 2013-9-9

[6]
Modification of hematopoietic stem/progenitor cells with CD19-specific chimeric antigen receptors as a novel approach for cancer immunotherapy.

Hum Gene Ther. 2013-10

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Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma.

Mol Ther. 2013-8-13

[8]
Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy.

Nat Biotechnol. 2013-8-11

[9]
Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology.

Immunity. 2013-7-25

[10]
Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells.

Clin Cancer Res. 2013-7-19

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