T-cell transfer; adenovirus; cellular therapy; central nervous system; cytomegalovirus; encephalitis; immune therapy; multiple sclerosis; progressive multifocal leukoencephalopathy; viral infections; virus-specific T-cells; Antiviral Agents; Humans; Central Nervous System; Antiviral Agents/therapeutic use; Cell- and Tissue-Based Therapy; Leukoencephalopathy, Progressive Multifocal; Cytomegalovirus Infections; Opportunistic Infections; Central Nervous System Diseases/therapy; Central Nervous System Diseases; Infectious Diseases; Virology
Abstract :
[en] Opportunistic viral infections of the central nervous system represent a significant cause of morbidity and mortality among an increasing number of immunocompromised patients. Since antiviral treatments are usually poorly effective, the prognosis generally relies on the ability to achieve timely immune reconstitution. Hence, strategies aimed at reinvigorating antiviral immune activity have recently emerged. Among these, virus-specific T-cells are increasingly perceived as a principled and valuable tool to treat opportunistic viral infections. Here we briefly discuss how to develop and select virus-specific T-cells, then review their main indications in central nervous system infections, including progressive multifocal leukoencephalopathy, CMV infection, and adenovirus infection. We also discuss their potential interest in the treatment of progressive multiple sclerosis, or EBV-associated central nervous system inflammatory disease. We finish with the key future milestones of this promising treatment strategy.
Disciplines :
Neurology
Author, co-author :
Lambert, Nicolas ; Université de Liège - ULiège > Département de géoressources, géotechnologies et matériaux de constructions > Géomécanique et géologie de l'ingénieur
El Moussaoui, Majdouline ; Centre Hospitalier Universitaire de Liège - CHU > > Service des maladies infectieuses - médecine interne
Baron, Frédéric ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'hématologie clinique
Maquet, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > > Service de neurologie
Darcis, Gilles ; Centre Hospitalier Universitaire de Liège - CHU > > Service des maladies infectieuses - médecine interne
Language :
English
Title :
Virus-Specific T-Cell Therapy for Viral Infections of the Central Nervous System: A Review.
Publication date :
06 July 2023
Journal title :
Viruses
eISSN :
1999-4915
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
Pruitt A.A. Central Nervous System Infections in Immunocompromised Patients Curr. Neurol. Neurosci. Rep. 2021 21 37 10.1007/s11910-021-01119-w 34037866
Sonneville R. Magalhaes E. Meyfroidt G. Central nervous system infections in immunocompromised patients Curr. Opin. Crit. Care 2017 23 128 133 10.1097/MCC.0000000000000397 28169858
Joly M. Conte C. Cazanave C. Le Moing V. Tattevin P. Delobel P. Sommet A. Martin-Blondel G. Progressive multifocal leukoencephalopathy: Epidemiology and spectrum of predisposing conditions Brain 2023 146 349 358 10.1093/brain/awac237
Nath A. Tyler K.L. Novel approaches and challenges to treatment of central nervous system viral infections Ann. Neurol. 2013 74 412 422 10.1002/ana.23988
Lambert N. El Moussaoui M. Maquet P. Immune checkpoint inhibitors for progressive multifocal leukoencephalopathy: Identifying relevant outcome factors Eur. J. Neurol. 2021 28 3814 3819 10.1111/ene.15021 34251719
Mapunda J.A. Tibar H. Regragui W. Engelhardt B. How Does the Immune System Enter the Brain? Front. Immunol. 2022 13 805657 10.3389/fimmu.2022.805657
Sallusto F. Impellizzieri D. Basso C. Laroni A. Uccelli A. Lanzavecchia A. Engelhardt B. T-cell trafficking in the central nervous system Immunol. Rev. 2012 248 216 227 10.1111/j.1600-065X.2012.01140.x
Korn T. Kallies A. T cell responses in the central nervous system Nat. Rev. Immunol. 2017 17 179 194 10.1038/nri.2016.144
Papadopoulos E.B. Ladanyi M. Emanuel D. Mackinnon S. Boulad F. Carabasi M.H. Castro-Malaspina H. Childs B.H. Gillio A.P. Small T.N. Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation N. Engl. J. Med. 1994 330 1185 1191 10.1056/NEJM199404283301703
Leen A.M. Tripic T. Rooney C.M. Challenges of T cell therapies for virus-associated diseases after hematopoietic stem cell transplantation Expert Opin. Biol. Ther. 2010 10 337 351 10.1517/14712590903456003
Walter E.A. Greenberg P.D. Gilbert M.J. Finch R.J. Watanabe K.S. Thomas E.D. Riddell S.R. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor N. Engl. J. Med. 1995 333 1038 1044 10.1056/NEJM199510193331603 7675046
Riddell S.R. Watanabe K.S. Goodrich J.M. Li C.R. Agha M.E. Greenberg P.D. Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones Science 1992 257 238 241 10.1126/science.1352912 1352912
Riddell S.R. Greenberg P.D. The use of anti-CD3 and anti-CD28 monoclonal antibodies to clone and expand human antigen-specific T cells J. Immunol. Methods 1990 128 189 201 10.1016/0022-1759(90)90210-M
Einsele H. Roosnek E. Rufer N. Sinzger C. Riegler S. Löffler J. Grigoleit U. Moris A. Rammensee H.G. Kanz L. Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy Blood 2002 99 3916 3922 10.1182/blood.V99.11.3916
Peggs K. Verfuerth S. Mackinnon S. Induction of cytomegalovirus (CMV)-specific T-cell responses using dendritic cells pulsed with CMV antigen: A novel culture system free of live CMV virions Blood 2001 97 994 1000 10.1182/blood.V97.4.994 11159528
Manz R. Assenmacher M. Pflüger E. Miltenyi S. Radbruch A. Analysis and sorting of live cells according to secreted molecules, relocated to a cell-surface affinity matrix Proc. Natl. Acad. Sci. USA 1995 92 1921 1925 10.1073/pnas.92.6.1921
Brosterhus H. Brings S. Leyendeckers H. Manz R.A. Miltenyi S. Radbruch A. Assenmacher M. Schmitz J. Enrichment and detection of live antigen-specific CD4(+) and CD8(+) T cells based on cytokine secretion Eur. J. Immunol. 1999 29 4053 4059 10.1002/(SICI)1521-4141(199912)29:12<4053::AID-IMMU4053>3.0.CO;2-C
Neill L. Peggs K. Cell therapy for cytomegalovirus infection Expert Opin. Biol. Ther. 2021 21 649 659 10.1080/14712598.2021.1857720
Tzannou I. Papadopoulou A. Naik S. Leung K. Martinez C.A. Ramos C.A. Carrum G. Sasa G. Lulla P. Watanabe A. et al. Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation J. Clin. Oncol. 2017 35 3547 3557 10.1200/JCO.2017.73.0655
Olson A. Lin R. Marin D. Rafei H. Bdaiwi M.H. Thall P.F. Basar R. Abudayyeh A. Banerjee P. Aung F.M. et al. Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation J. Clin. Oncol. 2021 39 2710 2719 10.1200/JCO.20.02608
Peterson C.W. Kiem H.P. Cell and Gene Therapy for HIV Cure Curr. Top Microbiol. Immunol. 2018 417 211 248 10.1007/82_2017_71 29256135
Toor S.M. Saleh R. Sasidharan Nair V. Taha R.Z. Elkord E. T-cell responses and therapies against SARS-CoV-2 infection Immunology 2021 162 30 43 10.1111/imm.13262 32935333
Fujita Y. Leen A.M. Sun J. Nakazawa Y. Yvon E. Heslop H.E. Brenner M.K. Rooney C.M. Exploiting cytokine secretion to rapidly produce multivirus-specific T cells for adoptive immunotherapy J. Immunother. 2008 31 665 674 10.1097/CJI.0b013e318181b4bd
Gerdemann U. Vera J.F. Rooney C.M. Leen A.M. Generation of multivirus-specific T cells to prevent/treat viral infections after allogeneic hematopoietic stem cell transplant J. Vis. Exp. 2011 51 2736 10.3791/2736
Kállay K. Kassa C. Réti M. Karászi É. Sinkó J. Goda V. Stréhn A. Csordás K. Horváth O. Szederjesi A. et al. Early Experience With CliniMACS Prodigy CCS (IFN-gamma) System in Selection of Virus-specific T Cells From Third-party Donors for Pediatric Patients With Severe Viral Infections After Hematopoietic Stem Cell Transplantation J. Immunother. 2018 41 158 163 10.1097/CJI.0000000000000197
Cortese I. Reich D.S. Nath A. Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease Nat. Rev. Neurol. 2021 17 37 51 10.1038/s41582-020-00427-y 33219338
Boumaza X. Bonneau B. Roos-Weil D. Pinnetti C. Rauer S. Nitsch L. Del Bello A. Jelcic I. Sühs K.W. Gasnault J. et al. Progressive Multifocal Leukoencephalopathy Treated by Immune Checkpoint Inhibitors Ann. Neurol. 2023 93 257 270 10.1002/ana.26512
Lambert N. Dauby S. Dive D. Sadzot B. Maquet P. Atezolizumab Treatment for Progressive Multifocal Leukoencephalopathy Emerg. Infect. Dis. 2022 28 253 256 10.3201/eid2801.204809
Lambert N. El Moussaoui M. Ritacco C. Ritacco C. Moïse M. Paulus A. Delvenne P. Baron F. Sadzot B. Maquet P. Killing Two Birds With One Stone: Effective Control of Both Non-Small Cell Lung Cancer and Progressive Multifocal Leukoencephalopathy with Atezolizumab, A Case Report Front. Immunol. 2022 13 889148 10.3389/fimmu.2022.889148
Cortese I. Muranski P. Enose-Akahata Y. Ha S.K. Smith B. Monaco M. Ryschkewitsch C. Majof E.O. Ohayon J. Schindler M. et al. Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy N. Engl. J. Med. 2019 380 1597 1605 10.1056/NEJMoa1815039
Lajaunie R. Mainardi I. Gasnault J. Rousseau V. Tarantino A.G. Sommet A. Cinque P. Martin-Blondel G. PML study group Outcome of Progressive Multifocal Leukoencephalopathy Treated by Interleukin-7 Ann. Neurol. 2022 91 496 505 10.1002/ana.26307 35072281
Möhn N. Grote-Levi L. Hopfner F. Eiz-Vesper B. Maecker-Kolhoff B. Warnke C. Sühs K.W. Wattjes M.P. Höglinger G.U. Skripuletz T. Innovative therapeutic concepts of progressive multifocal leukoencephalopathy J. Neurol. 2022 269 2403 2413 10.1007/s00415-021-10952-5 34994851
Balduzzi A. Lucchini G. Hirsch H.H. Basso S. Cioni M. Rovelli A. Zincone A. Grimaldi M. Corti P. Bonanomi S. et al. Polyomavirus JC-targeted T-cell therapy for progressive multiple leukoencephalopathy in a hematopoietic cell transplantation recipient Bone Marrow Transpl. 2011 46 987 992 10.1038/bmt.2010.221
Muftuoglu M. Olson A. Marin D. Ahmed S. Mulanovich V. Tummala S. Chi T.L. Ferrajoli A. Kaur I. Li L. et al. Allogeneic BK Virus-Specific T Cells for Progressive Multifocal Leukoencephalopathy N. Engl. J. Med. 2018 379 1443 1451 10.1056/NEJMoa1801540
Krymskaya L. Sharma M.C. Martinez J. Haq W. Huang E.C. Limaye A.P. Diamond D.J. Lacey S.F. Cross-reactivity of T lymphocytes recognizing a human cytotoxic T-lymphocyte epitope within BK and JC virus VP1 polypeptides J. Virol. 2005 79 11170 11178 10.1128/JVI.79.17.11170-11178.2005 16103168
Cantalupo P. Doering A. Sullivan C.S. Pal A. Peden K.W. Lewis A.M. Pipas J.M. Complete nucleotide sequence of polyomavirus SA12 J. Virol. 2005 79 13094 13104 10.1128/JVI.79.20.13094-13104.2005
Li J. Melenhorst J. Hensel N. Rezvani K. Sconocchia G. Kilical Y. Hou J. Curfman B. Major E. Barrett A.J. T-cell responses to peptide fragments of the BK virus T antigen: Implications for cross-reactivity of immune response to JC virus J. Gen. Virol. 2006 87 Pt 10 2951 2960 10.1099/vir.0.82094-0
Koralnik I.J. Du Pasquier R.A. Kuroda M.J. Schmitz J.E. Dang X. Zheng Y. Lifton M. Letvin N.L. Association of prolonged survival in HLA-A2+ progressive multifocal leukoencephalopathy patients with a CTL response specific for a commonly recognized JC virus epitope J. Immunol. 2002 168 499 504 10.4049/jimmunol.168.1.499
Cortese I. Beck E.S. Al-Louzi O. Ohayon J. Andrada F. Osuorah I. Dwyer J. Billioux B.J. Dargah-Zada N. Schindler M.K. et al. BK virus-specific T cells for immunotherapy of progressive multifocal leukoencephalopathy: An open-label, single-cohort pilot study Lancet Neurol. 2021 20 639 652 10.1016/S1474-4422(21)00174-5
Berzero G. Basso S. Stoppini L. Palermo A. Pichiecchio A. Paoletti M. Lucev F. Gerevini S. Rossi A. Vegezzi E. et al. Adoptive Transfer of JC Virus-Specific T Lymphocytes for the Treatment of Progressive Multifocal Leukoencephalopathy Ann. Neurol. 2021 89 769 779 10.1002/ana.26020
Wicklein R. Heidegger S. Verbeek M. Eiz-Vesper B. Maecker-Kolhoff B. Kirschke J.S. Page A. Korn T. Hemmer B. Deschauer M. Combined Treatment With Pembrolizumab and Allogenic BK Virus-Specific T Cells in Progressive Multifocal Leukoencephalopathy: A Case Report Neurol. Neuroimmunol. Neuroinflamm. 2021 8 e1042 10.1212/NXI.0000000000001042
Hopfner F. Möhn N. Eiz-Vesper B. Ahmed S. Mulanovich V. Tummala S. Chi T.L. Ferrajoli A. Kaur I. Li L. et al. Allogeneic BK Virus-Specific T-Cell Treatment in 2 Patients With Progressive Multifocal Leukoencephalopathy Neurol. Neuroimmunol. Neuroinflamm. 2021 8 e1020 10.1212/NXI.0000000000001020
Steinhardt M.J. Wiercinska E. Pham M. Grigoleit G.U. Mazzoni A. Da-Via M. Zhou X. Meckel K. Nickel K. Duell J. et al. Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes J. Transl. Med. 2020 18 177 10.1186/s12967-020-02337-5
Rubinstein J.D. Jodele S. Heyenbruch D. Wilhelm J. Thomas S. Lutzko C. Zhu X. Leemhuis T. Cancelas J.A. Keller M. et al. Off-the-Shelf Third-Party Virus-Specific T Cell Therapy to Treat JC Polyomavirus Infection in Hematopoietic Stem Cell Transplantation Recipients Transpl. Cell Ther. 2022 28 e1 e116 10.1016/j.jtct.2021.11.005
Peghin M. Castaldo N. Tascini C. Bassetti M. Graziano E. Givone F. Savignano C. De Colle M.C. Bove T. Pipan C. et al. Successful JC virus-targeted T-cell therapy for progressive multifocal leukoencephalopathy in a lung transplant recipient J. Heart Lung Transpl. 2022 41 991 996 10.1016/j.healun.2022.04.001 35595631
Tian X. Jiang Z. Ma Q. Liu Q. Lu X. Liu W. Liao X. Zhou R. Su X. Luo Q. Prevalence of neutralizing antibodies to common respiratory viruses in intravenous immunoglobulin and in healthy donors in southern China J. Thorac. Dis. 2016 8 803 812 10.21037/jtd.2016.03.29 27162653
Lion T. Adenovirus persistence, reactivation, and clinical management FEBS Lett. 2019 593 3571 3582 10.1002/1873-3468.13576
Lion T. Adenovirus infections in immunocompetent and immunocompromised patients Clin. Microbiol. Rev. 2014 27 441 462 10.1128/CMR.00116-13
Sedláček P. Petterson T. Robin M. Sivaprakasam P. Vainorius E. Brundage T. Chandak A. Mozaffari E. Nichols G. Voigt S. Incidence of Adenovirus Infection in Hematopoietic Stem Cell Transplantation Recipients: Findings from the Advance Study Biol. Blood Marrow Transpl. 2019 25 810 818 10.1016/j.bbmt.2018.12.753
Cesaro S. Porta F. Adenovirus Infection in Pediatric Hematopoietic Cell Transplantation: A Challenge Still Open for Survival J. Clin. Med. 2022 11 4827 10.3390/jcm11164827 36013066
Lynch J.P. 3rd Kajon A.E. Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in Treatment and Prevention Semin. Respir. Crit. Care Med. 2016 37 586 602 10.1055/s-0036-1584923 27486739
La Rosa A.M. Champlin R.E. Mirza N. Gajewski J. Giralt S. Rolston K.V. Raad I. Jacobson K. Kontoyiannis D. Elting L. et al. Adenovirus infections in adult recipients of blood and marrow transplants Clin. Infect. Dis. 2001 32 871 876 10.1086/319352 11247710
Schwartz K.L. Richardson S.E. MacGregor D. Mahant S. Raghuram K. Bitnun A. Adenovirus-Associated Central Nervous System Disease in Children J. Pediatr. 2019 205 130 137 10.1016/j.jpeds.2018.09.036
Campbell D. Wong G.S. Park H. McLeod G. An Adult Case of Adenovirus-Associated Acute Disseminated Encephalomyelitis Case Rep. Infect Dis. 2023 2023 5528198 10.1155/2023/5528198
Huang Y.C. Huang S.L. Chen S.P. Huang Y.L. Huang C.G. Tsao K.C. Lin T.Y. Adenovirus infection associated with central nervous system dysfunction in children J. Clin. Virol. 2013 57 300 304 10.1016/j.jcv.2013.03.017 23619053
Matthes-Martin S. Boztug H. Lion T. Diagnosis and treatment of adenovirus infection in immunocompromised patients Expert Rev. Anti. Infect Ther. 2013 11 1017 1028 10.1586/14787210.2013.836964
Kampmann B. Cubitt D. Walls T. Naik P. Depala M. Samarasinghe S. Robson D. Hassan A. Rao K. Gaspar H. et al. Improved outcome for children with disseminated adenoviral infection following allogeneic stem cell transplantation Br. J. Haematol. 2005 130 595 603 10.1111/j.1365-2141.2005.05649.x
Hiwarkar P. Kosulin K. Cesaro S. Mikulska M. Styczynski J. Wynn R. Lion T. Management of adenovirus infection in patients after haematopoietic stem cell transplantation: State-of-the-art and real-life current approach: A position statement on behalf of the Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation Rev. Med. Virol. 2018 28 e1980 10.1002/rmv.1980
Lopez S.M.C. Michaels M.G. Green M. Adenovirus infection in pediatric transplant recipients: Are effective antiviral agents coming our way? Curr. Opin. Organ Transpl. 2018 23 395 399 10.1097/MOT.0000000000000542
Studahl M. Lindquist L. Eriksson B.M. Günther G. Bengner M. Franzen-Röhl E. Fohlman J. Bergström T. Aurelius E. Acute viral infections of the central nervous system in immunocompetent adults: Diagnosis and management Drugs 2013 73 131 158 10.1007/s40265-013-0007-5
Hiwarkar P. Amrolia P. Sivaprakasam P. Lum S.H. Doss H. O’Rafferty C. Petterson T. Patrick K. Silva J. Slatter M. et al. Brincidofovir is highly efficacious in controlling adenoviremia in pediatric recipients of hematopoietic cell transplant Blood 2017 129 2033 2037 10.1182/blood-2016-11-749721 28153824
Hill J.A. Nichols W.G. Marty F.M. Papanicolaou G.A. Brundage T.M. Lanier R. Zerr D.M. Boeckh M.J. Oral brincidofovir decreases the incidence of HHV-6B viremia after allogeneic HCT Blood 2020 135 1447 1451 10.1182/blood.2019004315
Hromas R. Clark C. Blanke C. Tricot G. Cornetta K. Hedderman A. Broun E.R. Failure of ribavirin to clear adenovirus infections in T cell-depleted allogeneic bone marrow transplantation Bone Marrow Transpl. 1994 14 663 664
Howard D.S. Phillips I.I.G.L. Reece D.E. Munn R.K. Henslee-Downey J. Pittard M. Barker M. Pomeroy C. Adenovirus infections in hematopoietic stem cell transplant recipients Clin. Infect. Dis. 1999 29 1494 1501 10.1086/313514 10585802
Chakrabarti S. Mautner V. Osman H. Collingham K.E. Fegan C.D. Klapper P.E. Moss P.A.H. Milligan D.W. Adenovirus infections following allogeneic stem cell transplantation: Incidence and outcome in relation to graft manipulation, immunosuppression, and immune recovery Blood 2002 100 1619 1627 10.1182/blood-2002-02-0377
Leen A.M. Rooney C.M. Adenovirus as an emerging pathogen in immunocompromised patients Br. J. Haematol. 2005 128 135 144 10.1111/j.1365-2141.2004.05218.x
Feuchtinger T. Lang P. Hamprecht K. Schumm M. Greil J. Jahn G. Niethammer D. Einsele H. Isolation and expansion of human adenovirus-specific CD4+ and CD8+ T cells according to IFN-gamma secretion for adjuvant immunotherapy Exp. Hematol. 2004 32 282 289 10.1016/j.exphem.2003.12.009
Feuchtinger T. Matthes-Martin S. Richard C. Lion T. Fuhrer M. Hamprecht K. Handgretinger R. Peters C. Schuster F.R. Beck R. et al. Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation Br. J. Haematol. 2006 134 64 76 10.1111/j.1365-2141.2006.06108.x 16803570
Feucht J. Opherk K. Lang P. Kayser S. Hartl L. Bethge W. Matthes-Martin S. Bader P. Albert M.H. Maecker-Kolhoff B. et al. Adoptive T-cell therapy with hexon-specific Th1 cells as a treatment of refractory adenovirus infection after, HSCT Blood 2015 125 1986 1994 10.1182/blood-2014-06-573725 25617426
Qian C. Campidelli A. Wang Y. Cai H. Venard V. Jeulin H. Dalle J.H. Pochon C. D’aveni M. Bruno B. et al. Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: A successful phase I/II multicenter clinical trial J. Hematol. Oncol. 2017 10 102 10.1186/s13045-017-0469-0
Rubinstein J.D. Zhu X. Leemhuis T. Pham G. Ray L. Emberesh S. Jodele S. Thomas S. Cancelas J.A. Bollard C.M. et al. Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted Blood Adv. 2021 5 3309 3321 10.1182/bloodadvances.2021004456
Bollard C.M. Rooney C.M. Heslop H.E. T-cell therapy in the treatment of post-transplant lymphoproliferative disease Nat. Rev. Clin. Oncol. 2012 9 510 519 10.1038/nrclinonc.2012.111 22801669
Leen A.M. Bollard C.M. Mendizabal A.M. Shpall E.J. Szabolcs P. Antin J.H. Kapoor N. Pai S.-Y. Rowley S.D. Kebriaei P. et al. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation Blood 2013 121 5113 5123 10.1182/blood-2013-02-486324
Ip W. Silva J.M.F. Gaspar H. Mitra A. Patel S. Rao K. Chiesa R. Amrolia P. Gilmour K. Ahsan G. et al. Multicenter phase 1/2 application of adenovirus-specific T cells in high-risk pediatric patients after allogeneic stem cell transplantation Cytotherapy 2018 20 830 838 10.1016/j.jcyt.2018.03.040
Creidy R. Moshous D. Touzot F. Elie C. Neven B. Gabrion A. Leruez-Ville M. Maury S. Ternaux B. Nisoy J. et al. Specific T cells for the treatment of cytomegalovirus and/or adenovirus in the context of hematopoietic stem cell transplantation J. Allergy Clin. Immunol. 2016 138 920 924.e3 10.1016/j.jaci.2016.03.032 27246524
Humar A. Snydman D. AST Infectious Diseases Community of Practice. Cytomegalovirus in solid organ transplant recipients Am. J. Transpl. 2009 9 (Suppl. S4) S78 S86 10.1111/j.1600-6143.2009.02897.x 20070700
Cook M. Briggs D. Craddock C. Mahendra P. Milligan D. Fegan C. Darbyshire P. Lawson S. Boxall E. Moss P. et al. Donor KIR genotype has a major influence on the rate of cytomegalovirus reactivation following T-cell replete stem cell transplantation Blood 2006 107 1230 1232 10.1182/blood-2005-03-1039
Schwarcz L. Chen M.J. Vittinghoff E. Hsu L. Schwarcz S. Declining incidence of AIDS-defining opportunistic illnesses: Results from 16 years of population-based AIDS surveillance AIDS 2013 27 597 605 10.1097/QAD.0b013e32835b0fa2
Bowen E.F. Wilson P. Cope A. Sabin C. Griffiths P. Davey C. Johnson M. Emery V. Cytomegalovirus retinitis in AIDS patients: Influence of cytomegaloviral load on response to ganciclovir, time to recurrence and survival AIDS 1996 10 1515 1520 10.1097/00002030-199611000-00009
Einsele H. Ljungman P. Boeckh M. How I treat CMV reactivation after allogeneic hematopoietic stem cell transplantation Blood 2020 135 1619 1629 10.1182/blood.2019000956
Ueda Oshima M. Xie H. Zamora D. Flowers M.E. Hill G.R. Mielcarek M.B. Sandmaier B.M. Gooley T.A. Boeckh M.J. Impact of GVHD prophylaxis on CMV reactivation and disease after HLA-matched peripheral blood stem cell transplantation Blood Adv. 2023 7 1394 1403 10.1182/bloodadvances.2022009112
Roemhild A. Reinke P. Virus-specific T-cell therapy in solid organ transplantation Transpl. Int. 2016 29 515 526 10.1111/tri.12659 26284570
Reddy S.M. Winston D.J. Territo M.C. Schiller G.J. CMV central nervous system disease in stem-cell transplant recipients: An increasing complication of drug-resistant CMV infection and protracted immunodeficiency Bone Marrow Transpl. 2010 45 979 984 10.1038/bmt.2010.35 20190836
Maschke M. Kastrup O. Diener H.C. CNS manifestations of cytomegalovirus infections: Diagnosis and treatment CNS Drugs 2002 16 303 315 10.2165/00023210-200216050-00003
Schmidt-Hieber M. Schwender J. Heinz W.J. Zabelina T. Kühl J.S. Mousset S. Schüttrumpf S. Junghanss C. Silling G. Basara N. et al. Viralence-phalitis after allogeneic stem cell transplantation: A rare complication with distinct characteristics of different causative agents Haematologica 2011 96 142 149 10.3324/haematol.2010.029876 20851868
Chen S.J. Wang S.C. Chen Y.C. Antiviral Agents as Therapeutic Strategies Against Cytomegalovirus Infections Viruses 2019 12 21 10.3390/v12010021
Baghban A. Malinis M. Ganciclovir and foscarnet dual-therapy for cytomegalovirus encephalitis: A case report and review of the literature J. Neurol. Sci. 2018 15 28 36 10.1016/j.jns.2018.02.029
Limaye A.P. Babu T.M. Boeckh M. Progress and Challenges in the Prevention, Diagnosis, and Management of Cytomegalovirus Infection in Transplantation Clin. Microbiol. Rev. 2020 34 e00043-19 10.1128/CMR.00043-19
Shigle T.L. Handy V.W. Chemaly R.F. Letermovir and its role in the prevention of cytomegalovirus infection in seropositive patients receiving an allogeneic hematopoietic cell transplant Ther. Adv. Hematol. 2020 11 2040620720937150 10.1177/2040620720937150
Hantz S. Garnier-Geoffroy F. Mazeron M.C. Garrigue I. Merville P. Mengelle C. Rostaing L. Saint Marcoux F. Essig M. Rerolle J.-P. et al. Drug-resistant cytomegalovirus in transplant recipients: A French cohort study J. Antimicrob. Chemother. 2010 65 2628 2640 10.1093/jac/dkq368
Shmueli E. Or R. Shapira M.Y. Resnick I.B. Caplan O. Bdolah-Abram T. Wolf D.G. High rate of cytomegalovirus drug resistance among patients receiving preemptive antiviral treatment after haploidentical stem cell transplantation J. Infect. Dis. 2014 209 557 561 10.1093/infdis/jit475 23983215
Ouellette C.P. Adoptive Immunotherapy for Prophylaxis and Treatment of Cytomegalovirus Infection Viruses 2022 14 2370 10.3390/v14112370
Feuchtinger T. Opherk K. Bethge W.A. Topp M.S. Schuster F.R. Weissinger E.M. Mohty M. Or R. Maschan M. Schumm M. et al. Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation Blood 2010 116 4360 4367 10.1182/blood-2010-01-262089
Pei X.Y. Zhao X.Y. Liu X.F. Mo X.-D. Lv M. Xu L.-P. Wang Y. Chang Y.-J. Zhang X.-H. Liu K.-Y. et al. Adoptive therapy with cytomegalovirus-specific T cells for cytomegalovirus infection after haploidentical stem cell transplantation and factors affecting efficacy Am. J. Hematol. 2022 97 762 769 10.1002/ajh.26535 35293011
Wang X. Yu U. Yang C. Wang C. Zhang X. Li Y. Li C. Wen F. Liu S. Cytomegalovirus (CMV)-specific cytotoxic T lymphocyte therapy resolve CMV diseases and refractory CMV infections in paediatric recipients of allogeneic haematopoietic stem cell transplantation Bone Marrow Transpl. 2022 57 271 275 10.1038/s41409-021-01499-0
Withers B. Blyth E. Clancy L.E. Yong A. Fraser C. Burgess J. Simms R. Brown R. Kliman D. Dubosq M.-C. et al. Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells Blood Adv. 2017 1 2193 2205 10.1182/bloodadvances.2017010223
Smith C. Beagley L. Rehan S. Neller M.A. Crooks P. Solomon M. Holmes-Liew C.-L. Holmes M. McKenzie S.C. Hopkins P. et al. Autologous Adoptive T-cell Therapy for Recurrent or Drug-resistant Cytomegalovirus Complications in Solid Organ Transplant Recipients: A Single-arm Open-label Phase I Clinical Trial Clin. Infect. Dis. 2019 68 632 640 10.1093/cid/ciy549 29982441
Prockop S.E. Hasan A. Doubrovina E. Dahi P.B. Rodriguez-Sanchez I. Curry M. Mauguen A. Papanicolaou G.A. Su Y. Yao J. et al. Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant J. Clin. Invest. 2023 133 e165476 10.1172/JCI165476
Alonso L. Rudilla F. Gimeno R. Codinach M. Blanco M. Querol S. Diaz de Heredia C. Successful treatment of post-transplant CMV meningoencephalitis with third-party CMV virus-specific T cells: Lessons learned Pediatr. Transpl. 2019 23 e13584 10.1111/petr.13584
Ke P. Bao X. Zhou J. Li X. Zhuang J. He X. Wu D. Zhang X. Ma X. Donor CMV-specific cytotoxic T lymphocytes successfully treated drug-resistant cytomegalovirus encephalitis after allogeneic hematopoietic stem cell transplantation Hematology 2020 25 43 47 10.1080/16078454.2019.1710945
Micklethwaite K. Hansen A. Foster A. Snape E. Antonenas V. Sartor M. Shaw P. Bradstock K. Gottlieb D. Ex vivo expansion and prophylactic infusion of CMV-pp65 peptide-specific cytotoxic T-lymphocytes following allogeneic hematopoietic stem cell transplantation Biol. Blood Marrow Transpl. 2007 13 707 714 10.1016/j.bbmt.2007.02.004 17531781
Engstrand M. Lidehall A.K. Totterman T.H. Herrman B. Eriksson B.M. Korsgren O. Cellular responses to cytomegalovirus in immunosuppressed patients: Circulating CD8+ T cells recognizing CMVpp65 are present but display functional impairment Clin. Exp. Immunol. 2003 132 96 104 10.1046/j.1365-2249.2003.02098.x
Walton C. King R. Rechtman L. Kaye W. Leray E. Marrie R.A. Robertson N. La Rocca N. Uitdehaag B. van der Mei I. et al. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition Mult. Scler. 2020 26 1816 1821 10.1177/1352458520970841 33174475
McGinley M.P. Goldschmidt C.H. Rae-Grant A.D. Diagnosis and Treatment of Multiple Sclerosis: A Review JAMA 2021 325 765 779 10.1001/jama.2020.26858
Wong Y. Meehan M.T. Burrows S.R. Doolan D.L. Miles J.J. Estimating the global burden of Epstein-Barr virus-related cancers J. Cancer Res. Clin. Oncol. 2022 148 31 46 10.1007/s00432-021-03824-y
Shannon-Lowe C. Rickinson A. The Global Landscape of EBV-Associated Tumors Front. Oncol. 2019 9 713 10.3389/fonc.2019.00713 31448229
Smith C. Khanna R. Adoptive T-cell therapy targeting Epstein-Barr virus as a treatment for multiple sclerosis Clin. Transl. Immunol. 2023 12 e1444 10.1002/cti2.1444
Thorley-Lawson D.A. Hawkins J.B. Tracy S.I. Shapiro M. The pathogenesis of Epstein-Barr virus persistent infection Curr. Opin. Virol. 2013 3 227 232 10.1016/j.coviro.2013.04.005
Arvin A. Campadelli-Fiume G. Mocarski E. Moore P.S. Roizman B. Whitley R. Yamanishi K. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis Cambridge University Press Cambridge, UK 2007
Young L. Alfieri C. Hennessy K. Evans H. O’Hara C. Anderson K.C. Ritz J. Shapiro R.S. Rickinson A. Kieff E. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease N. Engl. J. Med. 1989 321 1080 1085 10.1056/NEJM198910193211604
Hislop A.D. Taylor G.S. Sauce D. Rickinson A.B. Cellular responses to viral infection in humans: Lessons from Epstein-Barr virus Ann. Rev. Immunol. 2007 25 587 617 10.1146/annurev.immunol.25.022106.141553 17378764
Khanna R. Burrows S.R. Role of cytotoxic T lymphocytes in Epstein-Barr virus-associated diseases Ann. Rev. Microbiol. 2000 54 19 48 10.1146/annurev.micro.54.1.19
Smith C. Beagley L. Khanna R. Acquisition of polyfunctionality by Epstein-Barr virus-specific CD8+ T cells correlates with increased resistance to galectin-1-mediated suppression J. Virol. 2009 83 6192 6198 10.1128/JVI.00239-09 19357166
Bjornevik K. Cortese M. Healy B.C. Kuhle J. Mina M.J. Leng Y. Elledge S.J. Niebuhr D.W. Scher A.I. Munger K.L. et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis Science 2022 375 296 301 10.1126/science.abj8222 35025605
Serafini B. Rosicarelli B. Franciotta D. Magliozzi R. Reynolds R. Cinque P. Andreoni L. Trivedi P. Salvetti M. Faggioni A. et al. Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain J. Exp. Med. 2007 204 2899 2912 10.1084/jem.20071030
Aloisi F. Serafini B. Magliozzi R. Howell O.W. Reynolds R. Detection of Epstein-Barr virus and B-cell follicles in the multiple sclerosis brain: What you find depends on how and where you look Brain 2010 133 Pt 12 e157 10.1093/brain/awq223
Magliozzi R. Serafini B. Rosicarelli B. Chiappetta G. Veroni C. Reynolds R. Aloisi F. B-cell enrichment and Epstein-Barr virus infection in inflammatory cortical lesions in secondary progressive multiple sclerosis J. Neuropathol. Exp. Neurol. 2013 72 29 41 10.1097/NEN.0b013e31827bfc62
Serafini B. Severa M. Columba-Cabezas S. Rosicarelli B. Veroni C. Chiappetta G. Magliozzi R. Reynolds R. Coccia E.M. Aloisi F. Epstein-Barr virus latent infection and BAFF expression in B cells in the multiple sclerosis brain: Implications for viral persistence and intrathecal B-cell activation J. Neuropathol. Exp. Neurol. 2010 69 677 693 10.1097/NEN.0b013e3181e332ec
Hassani A. Corboy J.R. Al-Salam S. Khan G. Epstein-Barr virus is present in the brain of most cases of multiple sclerosis and may engage more than just B cells PLoS ONE 2018 13 e0192109 10.1371/journal.pone.0192109
Moreno M.A. Or-Geva N. Aftab B.T. Khanna R. Croze E. Steinman L. Han M.H. Molecular signature of Epstein-Barr virus infection in MS brain lesions Neurol. Neuroimmunol. Neuroinflamm. 2018 5 e466 10.1212/NXI.0000000000000466
Bar-Or A. Pender M.P. Khanna R. Steinman L. Hartung H.-P. Maniar T. Croze E. Aftab B.T. Giovannoni G. Joshi M.A. Epstein-Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies Trends Mol. Med. 2021 27 410 411 10.1016/j.molmed.2021.01.004 33608230
Pender M.P. Khanna R. Epstein-Barr virus-specific adoptive immunotherapy: A new horizon for multiple sclerosis treatment? Immunotherapy 2014 6 659 661 10.2217/imt.14.43
Smith C. Cooper L. Burgess M. Rist M. Webb N. Lambley E. Tellam J. Marlton P. Seymour J.F. Gandhi M. et al. Functional reversion of antigen-specific CD8+ T cells from patients with Hodgkin lymphoma following in vitro stimulation with recombinant polyepitope J. Immunol. 2006 177 4897 4906 10.4049/jimmunol.177.7.4897
Smith C. Økern G. Rehan S. Beagley L. Lee S.K. Aarvak T. Schjetne K.W. Khanna R. Ex vivo expansion of human T cells for adoptive immunotherapy using the novel Xeno-free CTS Immune Cell Serum Replacement Clin. Transl. Immunol. 2015 4 e31 10.1038/cti.2014.31
Pender M.P. Csurhes P.A. Smith C. Douglas N.L. Neller M.A. Matthews K.K. Beagley L. Rehan S. Crooks P. Hopkins T.J. et al. Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis JCI Insight 2018 3 e124714 Corrected in JCI Insight 2020, 5 10.1172/jci.insight.124714
Smith C. Lee V. Schuessler A. Beagley L. Rehan S. Tsang J. Li V. Tiu R. Smith D. Neller M.A. et al. Pre-emptive and therapeutic adoptive immunotherapy for nasopharyngeal carcinoma: Phenotype and effector function of T cells impact on clinical response Oncoimmunology 2017 6 e1273311 10.1080/2162402X.2016.1273311 28344888
Pender M.P. Csurhes P.A. Smith C. Beagley L. Hooper K.D. Raj M. Coulthard A. Burrows S.R. Khanna R. Epstein-Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis Mult. Scler. 2014 20 1541 1544 10.1177/1352458514521888
Ioannides Z.A. Csurhes P.A. Douglas N.L. Mackenroth G. Swayne A. Thompson K.M. Hopkins T.J. Green K.A. Blum S. Hooper K.D. et al. Sustained Clinical Improvement in a Subset of Patients With Progressive Multiple Sclerosis Treated With Epstein-Barr Virus-Specific T Cell Therapy Front. Neurol. 2021 12 652811 10.3389/fneur.2021.652811
Pender M.P. Hodgkinson S.J. Broadley S. Lindsey J.W. Ioannides Z.A. Bagert B. Gamelin L. Liu E. Ye W. Willmer J. et al. Updated open-label extension clinical data and new magnetization transfer ratio imaging data from a phase I study of ATA188, an off-the-shelf, allogeneic Epstein-Barr virus-targeted T-cell immunotherapy for progressive multiple sclerosis Mult. Scler. J. 2022 28 72
Simmons H.Z. Bazzell A.F. Dains J.E. Adverse Effects of Virus-Specific T-Cell Therapy: An Integrative Review J. Adv. Pract. Oncol. 2019 10 120 131
Cruz C.R. Hanley P.J. Liu H. Torrano V. Lin Y.F. Arce J.A. Gottschalk S. Savoldo B. Dotti G. Louis C.U. et al. Adverse events following infusion of T cells for adoptive immunotherapy: A 10-year experience Cytotherapy 2010 12 743 749 10.3109/14653241003709686 20429793
Rooney C.M. Smith C.A. Ng C.Y. Loftin S. Li C. Krance R.A. Brenner M.K. Heslop H.E. Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virusrelated lymphoproliferation Lancet 1995 345 9 13 10.1016/S0140-6736(95)91150-2
Peggs K.S. Verfuerth S. Pizzey A. Khan N. Guiver M. Moss P.A. Mackinnon S. Adoptive cellular therapy for early cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific T-cell lines Lancet 2003 362 1375 1377 10.1016/S0140-6736(03)14634-X
Leen A.M. Christin A. Myers G.D. Liu H. Cruz C.R. Hanley P.J. Kennedy-Nasser A.A. Leung K.S. Gee A.P. Krance R.A. et al. Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation Blood 2009 114 4283 4292 10.1182/blood-2009-07-232454 19700662
Houghtelin A. Bollard C.M. Virus-Specific T Cells for the Immunocompromised Patient Front. Immunol. 2017 8 1272 10.3389/fimmu.2017.01272
Melenhorst J.J. Castillo P. Hanley P.J. Keller M.D. Krance R.A. Margolin J. Leen A.M. Heslop H.E. Barrett A.J. Rooney C.M. et al. Graft versus leukemia response without graft-versus-host disease elicited by adoptively transferred multivirus-specific T-cells Mol. Ther. 2015 23 179 183 10.1038/mt.2014.192
Melenhorst J.J. Scheinberg P. Williams A. Ambrozak D.R. Keyvanfar K. Smith M. McCoy J.P. Jr. Hensel N.F. Douek D.C. Barrett A.J. Alloreactivity across HLA barriers is mediated by both naïve and antigen-experienced T cells Biol. Blood Marrow Transpl. 2011 17 800 809 10.1016/j.bbmt.2010.12.711 21215812
Koehne G. Hasan A. Doubrovina E. Prockop S. Tyler E. Wasilewski G. O’Reilly R.J. Immunotherapy with Donor T Cells Sensitized with Overlapping Pentadecapeptides for Treatment of Persistent Cytomegalovirus Infection or Viremia Biol. Blood Marrow Transpl. 2015 21 1663 1678 10.1016/j.bbmt.2015.05.015 26028505
Peggs K.S. Thomson K. Samuel E. Dyer G. Armoogum J. Chakraverty R. Pang K. Mackinnon S. Lowdell M.W. Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation Clin. Infect. Dis. 2011 52 49 57 10.1093/cid/ciq042
Fuji S. Kapp M. Einsele H. Alloreactivity of virus-specific T cells: Possible implication of graft-versus-host disease and graft-versus-leukemia effects Front. Immunol. 2013 4 330 10.3389/fimmu.2013.00330
Melenhorst J.J. Leen A.M. Bollard C.M. Quigley M.F. Price D.A. Rooney C.M. Brenner M.K. Barrett A.J. Heslop H.E. Allogeneic virus-specific T cells with HLA alloreactivity do not produce GVHD in human subjects Blood 2010 116 4700 4702 10.1182/blood-2010-06-289991 20709906
Papadopoulou A. Gerdemann U. Katari U.L. Tzannou I. Liu H. Martinez C. Leung K. Carrum G. Gee A.P. Vera J.F. et al. Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT Sci. Transl. Med. 2014 6 242ra83 10.1126/scitranslmed.3008825 24964991
Gallot G. Vollant S. Saïagh S. Clémenceau B. Vivien R. Cerato E. Bignon J.D. Ferrand C. Jaccard A. Vigouroux S. et al. T-cell therapy using a bank of EBV-specific cytotoxic T cells: Lessons from a phase I/II feasibility and safety study J. Immunother. 2014 37 170 179 10.1097/CJI.0000000000000031
Barker J.N. Doubrovina E. Sauter C. Jaroscak J.J. Perales M.A. Doubrovin M. Prockop S.E. Koehne G. O’Reilly R.J. Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes Blood 2010 116 5045 5049 10.1182/blood-2010-04-281873
Foster A.E. Dotti G. Lu A. Khalil M. Brenner M.K. Heslop H.E. Rooney C.M. Bollard C.M. Antitumor activity of EBV-specific T lymphocytes transduced with a dominant negative TGF-beta receptor J. Immunother. 2008 31 500 505 10.1097/CJI.0b013e318177092b 18463534
Blank C.U. Haining W.N. Held W. Hogan P.G. Kallies A. Lugli E. Lynn R.C. Philip M. Rao A. Restifo N.P. et al. Defining ‘T cell exhaustion’ Nat. Rev. Immunol. 2019 19 665 674 10.1038/s41577-019-0221-9
Menger L. Gouble A. Marzolini M.A. Pachnio A. Bergerhoff K. Henry J.Y. Smith J. Pule M. Moss P. Riddell S.R. et al. TALEN-mediated genetic inactivation of the glucocorticoid receptor in cytomegalovirus-specific T cells Blood 2015 126 2781 2789 10.1182/blood-2015-08-664755
Ricciardelli I. Brewin J. Lugthart G. Albon S.J. Pule M. Amrolia P.J. Rapid generation of EBV-specific cytotoxic T lymphocytes resistant to calcineurin inhibitors for adoptive immunotherapy Am. J. Transpl. 2013 13 3244 3252 10.1111/ajt.12475
De Angelis B. Dotti G. Quintarelli C. Huye L.E. Zhang L. Zhang M. Pane F. Heslop H.E. Brenner M.K. Rooney C.M. et al. Generation of Epstein-Barr virus-specific cytotoxic T lymphocytes resistant to the immunosuppressive drug tacrolimus (FK506) Blood 2009 114 4784 4791 10.1182/blood-2009-07-230482
