Genetic Ablation of HLA Class I, Class II, and the T-cell Receptor Enables Allogeneic T Cells to Be Used for Adoptive T-cell Therapy
Tóm tắt
Adoptive immunotherapy can induce sustained therapeutic effects in some cancers. Antitumor T-cell grafts are often individually prepared in vitro from autologous T cells, which requires an intensive workload and increased costs. The quality of the generated T cells can also be variable, which affects the therapy's antitumor efficacy and toxicity. Standardized production of antitumor T-cell grafts from third-party donors will enable widespread use of this modality if allogeneic T-cell responses are effectively controlled. Here, we generated HLA class I, HLA class II, and T-cell receptor (TCR) triple-knockout (tKO) T cells by simultaneous knockout of the B2M, CIITA, and TRAC genes through Cas9/sgRNA ribonucleoprotein electroporation. Although HLA-deficient T cells were targeted by natural killer cells, they persisted better than HLA-sufficient T cells in the presence of allogeneic peripheral blood mononuclear cells (PBMC) in immunodeficient mice. When transduced with a CD19 chimeric antigen receptor (CAR) and stimulated by tumor cells, tKO CAR-T cells persisted better when cultured with allogeneic PBMCs compared with TRAC and B2M double-knockout T cells. The CD19 tKO CAR-T cells did not induce graft-versus-host disease but retained antitumor responses. These results demonstrated the benefit of HLA class I, HLA class II, and TCR deletion in enabling allogeneic-sourced T cells to be used for off-the-shelf adoptive immunotherapy.
Từ khóa
Tài liệu tham khảo
Rosenberg, 2015, Adoptive cell transfer as personalized immunotherapy for human cancer, Science, 348, 62, 10.1126/science.aaa4967
Maude, 2014, Chimeric antigen receptor T cells for sustained remissions in leukemia, N Engl J Med, 371, 1507, 10.1056/NEJMoa1407222
Davila, 2014, Efficacy and toxicity management of 19–28z CAR T cell therapy in B cell acute lymphoblastic leukemia, Sci Transl Med, 6, 224ra25, 10.1126/scitranslmed.3008226
Schuster, 2017, Chimeric antigen receptor T cells in refractory B-cell lymphomas, N Engl J Med, 377, 2545, 10.1056/NEJMoa1708566
Morgan, 2006, Cancer regression in patients after transfer of genetically engineered lymphocytes, Science, 314, 126, 10.1126/science.1129003
Parkhurst, 2011, T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis, Mol Ther, 19, 620, 10.1038/mt.2010.272
Robbins, 2011, Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1, J Clin Oncol, 29, 917, 10.1200/JCO.2010.32.2537
Fraietta, 2018, Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia, Nat Med, 24, 563, 10.1038/s41591-018-0010-1
Kagoya, 2017, Transient stimulation expands superior antitumor T cells for adoptive therapy, JCI Insight, 2, e89580, 10.1172/jci.insight.89580
Sommermeyer, 2016, Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo, Leukemia, 30, 492, 10.1038/leu.2015.247
Xu, 2014, Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15, Blood, 123, 3750, 10.1182/blood-2014-01-552174
Torikai, 2016, Translational implications for off-the-shelf immune cells expressing chimeric antigen receptors, Mol Ther, 24, 1178, 10.1038/mt.2016.106
Hartwig, 2006, Depletion of alloreactive T cells via CD69: implications on antiviral, antileukemic and immunoregulatory T lymphocytes, Bone Marrow Transplant, 37, 297, 10.1038/sj.bmt.1705238
Solomon, 2005, Selective depletion of alloreactive donor lymphocytes: a novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation, Blood, 106, 1123, 10.1182/blood-2005-01-0393
Wehler, 2007, Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines, Blood, 109, 365, 10.1182/blood-2006-04-014100
Amrolia, 2006, Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation, Blood, 108, 1797, 10.1182/blood-2006-02-001909
Davies, 2010, Combining CD19 redirection and alloanergization to generate tumor-specific human T cells for allogeneic cell therapy of B-cell malignancies, Cancer Res, 70, 3915, 10.1158/0008-5472.CAN-09-3845
Cruz, 2013, 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, 122, 2965, 10.1182/blood-2013-06-506741
Marino, 2016, Allorecognition by T lymphocytes and allograft rejection, Front Immunol, 7, 582, 10.3389/fimmu.2016.00582
Qasim, 2017, Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells, Sci Transl Med, 9, eaaj2013, 10.1126/scitranslmed.aaj2013
Marcus, 2011, Redirected tumor-specific allogeneic T cells for universal treatment of cancer, Blood, 118, 975, 10.1182/blood-2011-02-334284
Bak, 2018, CRISPR/Cas9 genome editing in human hematopoietic stem cells, Nat Protoc, 13, 358, 10.1038/nprot.2017.143
Roth, 2018, Reprogramming human T cell function and specificity with non-viral genome targeting, Nature, 559, 405, 10.1038/s41586-018-0326-5
Seki, 2018, Optimized RNP transfection for highly efficient CRISPR/Cas9-mediated gene knockout in primary T cells, J Exp Med, 215, 985, 10.1084/jem.20171626
Eyquem, 2017, Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection, Nature, 543, 113, 10.1038/nature21405
Liu, 2017, CRISPR-Cas9-mediated multiplex gene editing in CAR-T cells, Cell Res, 27, 154, 10.1038/cr.2016.142
Poirot, 2015, Multiplex genome-edited T-cell manufacturing platform for "off-the-shelf" adoptive T-cell immunotherapies, Cancer Res, 75, 3853, 10.1158/0008-5472.CAN-14-3321
Ren, 2017, Multiplex genome editing to generate universal CAR T cells resistant to PD1 inhibition, Clin Cancer Res, 23, 2255, 10.1158/1078-0432.CCR-16-1300
Ren, 2017, A versatile system for rapid multiplex genome-edited CAR T cell generation, Oncotarget, 8, 17002, 10.18632/oncotarget.15218
Holling, 2002, Activated human T cells accomplish MHC class II expression through T cell-specific occupation of class II transactivator promoter III, J Immunol, 168, 763, 10.4049/jimmunol.168.2.763
Schooten, 2005, Lack of MHC-II expression in activated mouse T cells correlates with DNA methylation at the CIITA-PIII region, Immunogenetics, 57, 795, 10.1007/s00251-005-0051-8
Butler, 2012, Ex vivo expansion of human CD8+ T cells using autologous CD4+ T cell help, PLoS One, 7, e30229, 10.1371/journal.pone.0030229
Ory, 1996, A stable human-derived packaging cell line for production of high titer retrovirus/vesicular stomatitis virus G pseudotypes, PNAS, 93, 11400, 10.1073/pnas.93.21.11400
Holm, 2016, Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses, Nat Commun, 7, 10680, 10.1038/ncomms10680
Labun, 2016, CHOPCHOP v2: a web tool for the next generation of CRISPR genome engineering, Nucleic Acids Res, 44, W272, 10.1093/nar/gkw398
Montague, 2014, CHOPCHOP: a CRISPR/Cas9 and TALEN web tool for genome editing, Nucleic Acids Res, 42, W401, 10.1093/nar/gku410
Su, 2016, CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients, Sci Rep, 6, 20070, 10.1038/srep20070
Brinkman, 2014, Easy quantitative assessment of genome editing by sequence trace decomposition, Nucleic Acids Res, 42, e168, 10.1093/nar/gku936
Kagoya, 2018, A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects, Nat Med, 24, 352, 10.1038/nm.4478
Naserian, 2018, Simple, reproducible, and efficient clinical grading system for murine models of acute graft-versus-host disease, Front Immunol, 9, 10, 10.3389/fimmu.2018.00010
Gattinoni, 2011, A human memory T cell subset with stem cell-like properties, Nat Med, 17, 1290, 10.1038/nm.2446
Cieri, 2013, IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors, Blood, 121, 573, 10.1182/blood-2012-05-431718
Raval, 2001, Transcriptional coactivator, CIITA, is an acetyltransferase that bypasses a promoter requirement for TAF(II)250, Mol Cell, 7, 105, 10.1016/S1097-2765(01)00159-9
Deffrennes, 2001, Constitutive expression of MHC class II genes in melanoma cell lines results from the transcription of class II transactivator abnormally initiated from its B cell-specific promoter, J Immunol, 167, 98, 10.4049/jimmunol.167.1.98
Gourley, 2002, Aberrant expression of Fas ligand in mice deficient for the MHC class II transactivator, J Immunol, 168, 4414, 10.4049/jimmunol.168.9.4414
Sun, 2006, Human interleukin-15 improves engraftment of human T cells in NOD-SCID mice, Clin Vaccine Immunol, 13, 227, 10.1128/CVI.13.2.227-234.2006
Moretta, 1996, Receptors for HLA class-I molecules in human natural killer cells, Annu Rev Immunol, 14, 619, 10.1146/annurev.immunol.14.1.619
Daer, 2017, The Impact of chromatin dynamics on Cas9-mediated genome editing in human cells, ACS Synth Biol, 6, 428, 10.1021/acssynbio.5b00299
Ghassemi, 2018, Reducing ex vivo culture improves the antileukemic activity of chimeric antigen receptor (CAR) T cells, Cancer Immunol Res, 6, 1100, 10.1158/2326-6066.CIR-17-0405
Gornalusse, 2017, HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells, Nat Biotechnol, 35, 765, 10.1038/nbt.3860