Targeted multi-epitope switching enables straightforward positive/negative selection of CAR T cells.
Journal
Gene therapy
ISSN: 1476-5462
Titre abrégé: Gene Ther
Pays: England
ID NLM: 9421525
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
07
07
2020
accepted:
15
01
2021
revised:
11
12
2020
pubmed:
3
2
2021
medline:
28
10
2021
entrez:
2
2
2021
Statut:
ppublish
Résumé
Chimeric antigen receptor (CAR) T cell technology has enabled successfully novel concepts to treat cancer patients, with substantial remission rates in lymphoid malignancies. This cell therapy is based on autologous T lymphocytes that are genetically modified to express a CAR that recognizes tumor-associated antigens and mediates the elimination of the respective tumor cells. Current limitations include laborious manufacturing procedures as well as severe immunological side effects upon administration of CAR T cells. To address these limitations, we integrated RQR8, a multi-epitope molecule harboring a CD34 epitope and two CD20 mimotopes, alongside a CD19-targeting CAR, into the CD52 locus. Using CRISPR-Cas9 and adeno-associated virus-based donor vectors, some 60% of genome-edited T cells were CAR
Identifiants
pubmed: 33526841
doi: 10.1038/s41434-021-00220-6
pii: 10.1038/s41434-021-00220-6
pmc: PMC8455323
doi:
Substances chimiques
Antigens, CD19
0
Epitopes
0
Receptors, Antigen, T-Cell
0
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
602-612Informations de copyright
© 2021. The Author(s).
Références
Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368:1509–18.
pubmed: 23527958
pmcid: 4058440
doi: 10.1056/NEJMoa1215134
Majzner RG, Mackall CL. Clinical lessons learned from the first leg of the CAR T cell journey. Nat Med. 2019;25:1341–55.
pubmed: 31501612
doi: 10.1038/s41591-019-0564-6
Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–17.
pubmed: 25317870
pmcid: 4267531
doi: 10.1056/NEJMoa1407222
Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439–48.
pubmed: 29385370
pmcid: 5996391
doi: 10.1056/NEJMoa1709866
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531–44.
pubmed: 29226797
pmcid: 5882485
doi: 10.1056/NEJMoa1707447
Chavez JC, Bachmeier C, Kharfan-Dabaja MA. CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. Ther Adv Hematol. 2019;10:2040620719841581.
pubmed: 31019670
pmcid: 6466472
doi: 10.1177/2040620719841581
Martinez M, Moon EK. CAR T cells for solid tumors: new strategies for finding, infiltrating, and surviving in the tumor microenvironment. Front Immunol. 2019;10:128.
pubmed: 30804938
pmcid: 6370640
doi: 10.3389/fimmu.2019.00128
Elahi R, Khosh E, Tahmasebi S, Esmaeilzadeh A. Immune cell hacking: challenges and clinical approaches to create smarter generations of chimeric antigen receptor T cells. Front Immunol. 2018;9:1717.
pubmed: 30108584
pmcid: 6080612
doi: 10.3389/fimmu.2018.01717
Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood. 2016;127:3321–30.
pubmed: 27207799
pmcid: 4929924
doi: 10.1182/blood-2016-04-703751
Fitzgerald JC, Weiss SL, Maude SL, Barrett DM, Lacey SF, Melenhorst JJ, et al. Cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia. Crit Care Med. 2017;45:e124–31.
pubmed: 27632680
pmcid: 5452983
doi: 10.1097/CCM.0000000000002053
Milone MC, O’Doherty U. Clinical use of lentiviral vectors. Leukemia. 2018;32:1529–41.
pubmed: 29654266
pmcid: 6035154
doi: 10.1038/s41375-018-0106-0
Wang X, Riviere I. Clinical manufacturing of CAR T cells: foundation of a promising therapy. Mol Ther Oncolytics. 2016;3:16015.
pubmed: 27347557
pmcid: 4909095
doi: 10.1038/mto.2016.15
Levine BL, Miskin J, Wonnacott K, Keir C. Global manufacturing of CAR T cell therapy. Mol Ther Methods Clin Dev. 2017;4:92–101.
pubmed: 28344995
doi: 10.1016/j.omtm.2016.12.006
Hacein-Bey-Abina S, Garrigue A, Wang GP, Soulier J, Lim A, Morillon E, et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest. 2008;118:3132–42.
pubmed: 18688285
pmcid: 2496963
doi: 10.1172/JCI35700
Eyquem J, Mansilla-Soto J, Giavridis T, van der Stegen SJ, Hamieh M, Cunanan KM, et al. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature. 2017;543:113–7.
pubmed: 28225754
pmcid: 5558614
doi: 10.1038/nature21405
Jung IY, Lee J. Unleashing the therapeutic potential of CAR-T cell therapy using gene-editing technologies. Mol Cells. 2018;41:717–23.
pubmed: 30110720
pmcid: 6125425
MacLeod DT, Antony J, Martin AJ, Moser RJ, Hekele A, Wetzel KJ, et al. Integration of a CD19 CAR into the TCR alpha chain locus streamlines production of allogeneic gene-edited CAR T cells. Mol Ther. 2017;25:949–61.
pubmed: 28237835
pmcid: 5383629
doi: 10.1016/j.ymthe.2017.02.005
Qasim W, Zhan H, Samarasinghe S, Adams S, Amrolia P, Stafford S, et al. Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Sci Transl Med. 2017;9:eaaj2013.
pubmed: 28123068
doi: 10.1126/scitranslmed.aaj2013
Poirot L, Philip B, Schiffer-Mannioui C, Le Clerre D, Chion-Sotinel I, Derniame S, et al. Multiplex genome-edited T-cell manufacturing platform for “off-the-shelf” adoptive T-cell immunotherapies. Cancer Res. 2015;75:3853–64.
pubmed: 26183927
doi: 10.1158/0008-5472.CAN-14-3321
Rupp LJ, Schumann K, Roybal KT, Gate RE, Ye CJ, Lim WA, et al. CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells. Sci Rep. 2017;7:737.
pubmed: 28389661
pmcid: 5428439
doi: 10.1038/s41598-017-00462-8
Fehse B, Richters A, Putimtseva-Scharf K, Klump H, Li Z, Ostertag W, et al. CD34 splice variant: an attractive marker for selection of gene-modified cells. Mol Ther. 2000;1:448–56.
pubmed: 10933966
doi: 10.1006/mthe.2000.0068
Perosa F, Favoino E, Vicenti C, Merchionne F, Dammacco F. Identification of an antigenic and immunogenic motif expressed by two 7-mer rituximab-specific cyclic peptide mimotopes: implication for peptide-based active immunotherapy. J Immunol. 2007;179:7967–74.
pubmed: 18025245
doi: 10.4049/jimmunol.179.11.7967
Pescovitz MD. Rituximab, an anti-cd20 monoclonal antibody: history and mechanism of action. Am J Transplant. 2006;6:859–66.
pubmed: 16611321
doi: 10.1111/j.1600-6143.2006.01288.x
Philip B, Kokalaki E, Mekkaoui L, Thomas S, Straathof K, Flutter B, et al. A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Blood. 2014;124:1277–87.
pubmed: 24970931
doi: 10.1182/blood-2014-01-545020
Binder M, Otto F, Mertelsmann R, Veelken H, Trepel M. The epitope recognized by rituximab. Blood. 2006;108:1975–8.
pubmed: 16705086
doi: 10.1182/blood-2006-04-014639
Cornu TI, Mussolino C, Cathomen T. Refining strategies to translate genome editing to the clinic. Nat Med. 2017;23:415–23.
Walsh CE, Liu JM, Xiao X, Young NS, Nienhuis AW, Samulski RJ. Regulated high level expression of a human gamma-globin gene introduced into erythroid cells by an adeno-associated virus vector. Proc Natl Acad Sci USA. 1992;89:7257–61.
pubmed: 1323131
pmcid: 49685
doi: 10.1073/pnas.89.15.7257
Schneider D, Xiong Y, Wu D, Nlle V, Schmitz S, Haso W, et al. A tandem CD19/CD20 CAR lentiviral vector drives on-target and off-target antigen modulation in leukemia cell lines. J Immunother Cancer. 2017;5:42.
pubmed: 28515942
pmcid: 5433150
doi: 10.1186/s40425-017-0246-1
Dettmer V, Bloom K, Gross M, Weissert K, Aichele P, Ehl S, et al. Retroviral UNC13D gene transfer restores cytotoxic activity of T cells derived from familial hemophagocytic lymphohistiocytosis type 3 patients in vitro. Hum Gene Ther. 2019;30:975–84.
pubmed: 31032638
doi: 10.1089/hum.2019.025
van den Berg FT, Makoah NA, Ali SA, Scott TA, Mapengo RE, Mutsvunguma LZ, et al. AAV-mediated expression of broadly neutralizing and vaccine-like antibodies targeting the HIV-1 envelope V2 region. Mol Ther Methods Clin Dev. 2019;14:100–12.
pubmed: 31334303
pmcid: 6616373
doi: 10.1016/j.omtm.2019.06.002
Lock M, Alvira MR, Chen SJ, Wilson JM. Absolute determination of single-stranded and self-complementary adeno-associated viral vector genome titers by droplet digital PCR. Hum Gene Ther Methods. 2014;25:115–25.
pubmed: 24328707
doi: 10.1089/hgtb.2013.131
Osiak A, Radecke F, Guhl E, Radecke S, Dannemann N, Lutge F, et al. Selection-independent generation of gene knockout mouse embryonic stem cells using zinc-finger nucleases. PLoS ONE. 2011;6:e28911.
pubmed: 22194948
pmcid: 3237556
doi: 10.1371/journal.pone.0028911
Clement K, Rees H, Canver MC, Gehrke JM, Farouni R, Hsu JY, et al. CRISPResso2 provides accurate and rapid genome editing sequence analysis. Nat Biotechnol. 2019;37:224–6.
pubmed: 30809026
pmcid: 6533916
doi: 10.1038/s41587-019-0032-3
Hale G, Bright S, Chumbley G, Hoang T, Metcalf D, Munro AJ, et al. Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement. Blood. 1983;62:873–82.
pubmed: 6349718
doi: 10.1182/blood.V62.4.873.873
Chakrabarti S, Hale G, Waldmann H. Alemtuzumab (Campath-1H) in allogeneic stem cell transplantation: where do we go from here? Transplant Proc. 2004;36:1225–7.
pubmed: 15251298
doi: 10.1016/j.transproceed.2004.05.067
Muranski P, Boni A, Wrzesinski C, Citrin DE, Rosenberg SA, Childs R, et al. Increased intensity lymphodepletion and adoptive immunotherapy-how far can we go? Nat Clin Pract Oncol. 2006;3:668–81.
pubmed: 17139318
pmcid: 1773008
doi: 10.1038/ncponc0666
Pangalis GA, Dimopoulou MN, Angelopoulou MK, Tsekouras C, Vassilakopoulos TP, Vaiopoulos G, et al. Campath-1H (anti-CD52) monoclonal antibody therapy in lymphoproliferative disorders. Med Oncol. 2001;18:99–107.
pubmed: 11778765
doi: 10.1385/MO:18:2:99
Maloney DG, Grillo-Lopez AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, et al. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood. 1997;90:2188–95.
pubmed: 9310469
doi: 10.1182/blood.V90.6.2188
Edwards JC, Leandro MJ, Cambridge G. B-lymphocyte depletion therapy in rheumatoid arthritis and other autoimmune disorders. Biochem Soc Trans. 2002;30:824–8.
pubmed: 12196207
doi: 10.1042/bst0300824
Yu S, Yi M, Qin S, Wu K. Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity. Mol Cancer. 2019;18:125.
pubmed: 31429760
pmcid: 6701025
doi: 10.1186/s12943-019-1057-4
McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16:2825–33.
pubmed: 9704735
doi: 10.1200/JCO.1998.16.8.2825
Sather BD, Romano Ibarra GS, Sommer K, Curinga G, Hale M, Khan IF, et al. Efficient modification of CCR5 in primary human hematopoietic cells using a megaTAL nuclease and AAV donor template. Sci Transl Med. 2015;7:307ra156.
pubmed: 26424571
pmcid: 4790757
doi: 10.1126/scitranslmed.aac5530
Shah NN, Highfill SL, Shalabi H, Yates B, Jin J, Wolters PL, et al. CD4/CD8 T-cell selection affects chimeric antigen receptor (CAR) T-cell potency and toxicity: updated results from a phase I anti-CD22 CAR T-cell trial. J Clin Oncol. 2020;38:1938–50.
pubmed: 32286905
pmcid: 7280047
doi: 10.1200/JCO.19.03279
Gellhaus K, Cornu TI, Heilbronn R, Cathomen T. Fate of recombinant adeno-associated viral vector genomes during DNA double-strand break-induced gene targeting in human cells. Hum Gene Ther. 2010;21:543–53.
pubmed: 20021219
doi: 10.1089/hum.2009.167
Handel EM, Gellhaus K, Khan K, Bednarski C, Cornu TI, Muller-Lerch F, et al. Versatile and efficient genome editing in human cells by combining zinc-finger nucleases with adeno-associated viral vectors. Hum Gene Ther. 2012;23:321–9.
pubmed: 21980922
doi: 10.1089/hum.2011.140
Breton C, Clark PM, Wang L, Greig JA, Wilson JM. ITR-Seq, a next-generation sequencing assay, identifies genome-wide DNA editing sites in vivo following adeno-associated viral vector-mediated genome editing. BMC Genomics. 2020;21:239.
pubmed: 32183699
pmcid: 7076944
doi: 10.1186/s12864-020-6655-4
Hanlon KS, Kleinstiver BP, Garcia SP, Zaborowski MP, Volak A, Spirig SE, et al. High levels of AAV vector integration into CRISPR-induced DNA breaks. Nat Commun. 2019;10:4439.
pubmed: 31570731
pmcid: 6769011
doi: 10.1038/s41467-019-12449-2