Enhancing the effectiveness of y8 T cells by mRNA transfection of chimeric antigen receptors or bispecific T cell engagers

被引:11
作者
Becker, Scott A. [1 ]
Petrich, Brian G. [2 ]
Yu, Bing [2 ]
Knight, Kristopher A. [1 ]
Brown, Harrison C. [2 ]
Raikar, Sunil S. [3 ,4 ]
Doering, Christopher B. [1 ,3 ,4 ]
Spencer, H. Trent [1 ,3 ,4 ]
机构
[1] Emory Univ, Mol & Syst Pharmacol Program, Grad Div Biol & Biomed Sci, Atlanta, GA USA
[2] Express Therapeut Inc, Tucker, GA USA
[3] Emory Univ, Aflac Canc & Blood Disorders Ctr, Sch Med, Dept Pediat, Atlanta, GA 30322 USA
[4] Childrens Healthcare Atlanta, Atlanta, GA 30322 USA
关键词
ANTITUMOR-ACTIVITY; CYTOTOXICITY; LEUKEMIA; THERAPEUTICS; RECOGNITION; LYMPHOCYTES; INCREASE;
D O I
10.1016/j.omto.2023.05.007
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Adoptive cell therapy (ACT) utilizing yb T cells is becoming a promising option for the treatment of cancer, because it offers an off-the-shelf allogeneic product that is safe, potent, and clinically effective. Approaches to engineer or enhance immunecompetent cells for ACT, like expression of chimeric antigen receptors (CARs) or combination treatments with bispecific T cell engagers, have improved the specificity and cytotoxic potential of ACTs and have shown great promise in preclinical and clinical settings. Here, we test whether electroporation of yb T cells with CAR or secreted bispecific T cell engager (sBite) mRNA is an effective approach to improve the cytotoxicity of yb T cells. Using a CD19-specific CAR, approximately 60% of yb T cells are modified after mRNA electroporation and these cells show potent anticancer activity in vitro and in vivo against two CD19-positive cancer cell lines. In addition, expression and secretion of a CD19 sBite enhances yb T cell cytotoxicity, both in vitro and in vivo, and promotes killing of target cells by modified and unmodified yb T cells. Taken together, we show that transient transfection of yb T cells with CAR or sBite mRNA by electroporation can be an effective treatment platform as a cancer therapeutic.
引用
收藏
页码:145 / 157
页数:13
相关论文
共 61 条
[1]   Cross-presenting human γδ T cells induce robust CD8+ αβ T cell responses [J].
Brandes, Marlene ;
Willimann, Katharina ;
Bioley, Gilles ;
Levy, Nicole ;
Eberl, Matthias ;
Luo, Ming ;
Tampe, Robert ;
Levy, Frederic ;
Romero, Pedro ;
Moser, Bernhard .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (07) :2307-2312
[2]   Target-Cell-Directed Bioengineering Approaches for Gene Therapy of Hemophilia A [J].
Brown, Harrison C. ;
Zakas, Philip M. ;
George, Stephan N. ;
Parker, Ernest T. ;
Spencer, H. Trent ;
Doering, Christopher B. .
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT, 2018, 9 :57-69
[3]   Human serum albumin and chromatin condensation rescue ex vivo expanded γδ T cells from the effects of cryopreservation [J].
Burnham, Rebecca E. ;
Tope, Donald ;
Branella, Gianna ;
Williams, Erich ;
Doering, Christopher B. ;
Spencer, H. Trent .
CRYOBIOLOGY, 2021, 99 :78-87
[4]   Characterization of Donor Variability for γδ T Cell ex vivo Expansion and Development of an Allogeneic γδ T Cell Immunotherapy [J].
Burnham, Rebecca E. ;
Zoine, Jaquelyn T. ;
Story, Jamie Y. ;
Garimalla, Swetha N. ;
Gibson, Greg ;
Rae, Aaron ;
Williams, Erich ;
Bixby, Lisa ;
Archer, David ;
Doering, Christopher B. ;
Spencer, H. Trent .
FRONTIERS IN MEDICINE, 2020, 7
[5]   Efficient and Non-genotoxic RNA-Based Engineering of Human T Cells Using Tumor-Specific T Cell Receptors With Minimal TCR Mispairing [J].
Campillo-Davo, Diana ;
Fujiki, Fumihiro ;
Van den Bergh, Johan M. J. ;
De Reu, Hans ;
Smits, Evelien L. J. M. ;
Goossens, Herman ;
Sugiyama, Haruo ;
Lion, Eva ;
Berneman, Zwi N. ;
Van Tendeloo, Viggo .
FRONTIERS IN IMMUNOLOGY, 2018, 9
[6]   Stimulated γδ T Cells Increase the In Vivo Efficacy of Trastuzumab in HER-2+ Breast Cancer [J].
Capietto, Aude-Helene ;
Martinet, Ludovic ;
Fournie, Jean-Jacques .
JOURNAL OF IMMUNOLOGY, 2011, 187 (02) :1031-1038
[7]   Chimeric Antigen Receptor-Engineered Human Gamma Delta T Cells: Enhanced Cytotoxicity with Retention of Cross Presentation [J].
Capsomidis, Anna ;
Benthall, Gabriel ;
Van Acker, Heleen H. ;
Fisher, Jonathan ;
Kramer, Anne M. ;
Abeln, Zarah ;
Majani, Yvonne ;
Gileadi, Talia ;
Wallace, Rebecca ;
Gustafsson, Kenth ;
Flutter, Barry ;
Anderson, John .
MOLECULAR THERAPY, 2018, 26 (02) :354-365
[8]   The potential of adoptive transfer of γ9δ2 T cells to enhance blinatumomab's antitumor activity against B-cell malignancy [J].
Chen, Yun-Hsiang ;
Wang, Yun ;
Liao, Cheng-Hao ;
Hsu, Shu-Ching .
SCIENTIFIC REPORTS, 2021, 11 (01)
[9]   MICA engagement by human Vγ2Vδ2 T cells enhances their antigen-dependent effector function [J].
Das, H ;
Groh, V ;
Kuijl, C ;
Sugita, M ;
Morita, CT ;
Spies, T ;
Bukowski, JF .
IMMUNITY, 2001, 15 (01) :83-93
[10]  
de Weerdt I., 2021, Clin Cancer Res, V27, P1744, DOI [10.1158/1078-0432.CCR-20-4576, DOI 10.1158/1078-0432.CCR-20-4576]