Treatment of resistant viral infections after allogeneic hematopoietic stem cell transplantation using virus-specific T cells
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used in the treatment of malignant and non-malignant diseases. Patients treated with allo-HSCT receive immunosuppression, which lowers the organism’s immune response. This leaves a significant period during which the host is seriously deficient in T cell immunity. Viral infections are therefore one of the major causes of morbidity and mortality in these patients. Available prophylactic and preventive antiviral pharmacotherapies are often insufficient or limited due to toxicity, ineffectiveness, or the development of drug resistance, and additionally do not provide long-term protection or immunological memory.
A current extension of virostatic agents is the transplantation of antiviral immunity through adoptive transfer of virus-specific T cells (VSTs) against ADV, CMV, or EBV. Strategies that accelerate pathogen-specific immunity and T-cell regeneration may complement or replace available treatments.
Keywords: cell therapyallogeneic stem cell transplantationviral infectionslymphocytes Tvirus-specific T cells
References
- Ottaviano G, Chiesa R, Feuchtinger T, et al. Adoptive T cell therapy strategies for viral infections in patients receiving haematopoietic stem cell transplantation. Cells. 2019; 8(1): 47.
- Storek J. Immunological reconstitution after hematopoietic cell transplantation - its relation to the contents of the graft. Expert Opin Biol Ther. 2008; 8(5): 583–597.
- Gil L. Zakażenia wirusowe po transplantacji komórek krwiotwórczych. Acta Haematol Pol. 2013; 44(3): 245–250.
- Gratwohl A, Brand R, Frassoni F, et al. Acute and Chronic Leukemia Working Parties, Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: an EBMT analysis of lethal infectious complications and changes over calendar time. Bone Marrow Transplant. 2005; 36(9): 757–769.
- Kaeuferle T, Krauss R, Blaeschke F, et al. Strategies of adoptive T -cell transfer to treat refractory viral infections post allogeneic stem cell transplantation. J Hematol Oncol. 2019; 12(1): 13.
- Martin-Moreno PL, Panizo C. Update on posttransplant lymphoproliferative disease. Curr Opin Nephrol Hypertens. 2018; 27(6): 440–444.
- Bollard CM, Kuehnle I, Leen A, et al. Adoptive immunotherapy for posttransplantation viral infections. Biol Blood Marrow Transplant. 2004; 10(3): 143–155.
- Howard DS, Phillips II GL, Reece DE, et al. Adenovirus infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 1999; 29(6): 1494–1501.
- Styczyński J, Czyżewski K, Frączkiewicz J, et al. Zakażenia wirusowe u dzieci po przeszczepieniu komórek krwiotwórczych: raport 2016 Polskiej Pediatrycznej Grupy ds. Zakażeń Polskiego Towarzystwa Onkologii i Hematologii Dziecięcej. Acta Haematol Pol. 2017; 48(1): 23–27.
- Srinivasan A, Wang C, Srivastava DK, et al. Timeline, epidemiology, and risk factors for bacterial, fungal, and viral infections in children and adolescents after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013; 19(1): 94–101.
- Srinivasan A, McLaughlin L, Wang C, et al. Early infections after autologous hematopoietic stem cell transplantation in children and adolescents: the St. Jude experience. Transpl Infect Dis. 2014; 16(1): 90–97.
- Keller MD, Bollard CM. Virus-specific T-cell therapies for patients with primary immune deficiency. Blood. 2020; 135(9): 620–628.
- Boeckh M, Nichols WG, Papanicolaou G, et al. Cytomegalovirus in hematopoietic stem cell transplant recipients: Current status, known challenges, and future strategies. Biol Blood Marrow Transplant. 2003; 9(9): 543–558.
- El Chaer F, Shah DP, Chemaly RF. How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients. Blood. 2016; 128(23): 2624–2636.
- Marty FM, Ljungman PT, Chemaly RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med. 2017; 377(25): 2433–2444.
- Marty FM, Winston DJ, Chemaly RF, et al. SUPPRESS Trial Clinical Study Group, CMX001-201 Clinical Study Group. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013; 369(13): 1227–1236.
- Styczyński J. Prophylaxis vs preemptive therapy in prevention of CMV infection: new insight on prophylactic strategy after allogeneic hematopoietic cell transplantation. Acta Haematol Pol. 2020; 51(1): 17–23.
- Kuhn A, Puttkammer J, Madigan T, et al. Letermovir as cytomegalovirus prophylaxis in a pediatric cohort: a retrospective analysis. Transplant Cell Ther. 2023; 29(1): 62.e1–62.e4.
- Chen TT, David AP, Barthelmess EK, et al. Letermovir for cytomegalovirus prophylaxis in pediatric hematopoietic stem cell transplantation. Pediatr Blood Cancer. 2023; 70(11): e30608.
- César T, Le MP, Klifa R, et al. Letermovir for CMV prophylaxis in very high-risk pediatric hematopoietic stem cell transplantation recipients for inborn errors of immunity. J Clin Immunol. 2023; 44(1): 6.
- Ljungman P, de la Camara R, Robin C, et al. 2017 European Conference on Infections in Leukaemia group. Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis. 2019; 19(8): e260–e272.
- Cohen JM, Cooper N, Chakrabarti S, et al. EBV-related disease following haematopoietic stem cell transplantation with reduced intensity conditioning. Leuk Lymphoma. 2007; 48(2): 256–269.
- Cohen JI. Primary immunodeficiencies associated with EBV disease. Curr Top Microbiol Immunol. 2015; 390(Pt 1): 241–265.
- Grimley MS, Chemaly RF, Englund JA, et al. Brincidofovir for asymptomatic adenovirus viremia in pediatric and adult allogeneic hematopoietic cell transplant recipients: a randomized placebo-controlled phase II trial. Biol Blood Marrow Transplant. 2017; 23(3): 512–521.
- Hiwarkar P, Amrolia P, Sivaprakasam P, et al. United Kingdom Paediatric Bone Marrow Transplant Group. Brincidofovir is highly efficacious in controlling adenoviremia in pediatric recipients of hematopoietic cell transplant. Blood. 2017; 129(14): 2033–2037.
- Kaufman GP, Aksamit AJ, Klein CJ, et al. Progressive multifocal leukoencephalopathy: a rare infectious complication following allogeneic hematopoietic cell transplantation (HCT). Eur J Haematol. 2014; 92(1): 83–87.
- Philippe M, Ranchon F, Gilis L, et al. Cidofovir in the treatment of BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2016; 22(4): 723–730.
- Mohammadi Najafabadi M, Soleimani M, Ahmadvand M, et al. Treatment protocols for BK virus associated hemorrhagic cystitis after hematopoietic stem cell transplantation. Am J Blood Res. 2020; 10(5): 217–230.
- Harris KM, Davila BJ, Bollard CM, et al. Virus-specific T cells: current and future use in primary immunodeficiency disorders. J Allergy Clin Immunol Pract. 2019; 7(3): 809–818.
- Motta CM, Keller MD, Bollard CM. Applications of virus-specific T cell therapies post-BMT. Semin Hematol. 2023; 60(1): 10–19.
- Riddell SR, Watanabe KS, Goodrich JM, et al. Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science. 1992; 257(5067): 238–241.
- Riddell SR, Greenberg PD. The use of anti-CD3 and anti-CD28 monoclonal antibodies to clone and expand human antigen-specific T cells. J Immunol Methods. 1990; 128(2): 189–201.
- Rooney CM, Smith CA, Ng CY, et al. Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet. 1995; 345(8941): 9–13.
- Savoldo B, Heslop HE, Rooney CM, et al. Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients. Blood. 1998; 92(5): 1549–1555.
- Kállay K, Kassa C, Réti M, 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(3): 158–163.
- Khanna N, Stuehler C, Conrad B, et al. Generation of a multipathogen-specific T-cell product for adoptive immunotherapy based on activation-dependent expression of CD154. Blood. 2011; 118(4): 1121–1131.
- Zandvliet ML, van Liempt E, Jedema I, et al. Simultaneous isolation of CD8(+) and CD4(+) T cells specific for multiple viruses for broad antiviral immune reconstitution after allogeneic stem cell transplantation. J Immunother. 2011; 34(3): 307–319.
- Withers B, Blyth E, Clancy LE, 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(24): 2193–2205.
- Dadwal S, Shuster M, Myers G, et al. Posoleucel (ALVR105), an Off-the-Shelf, Multivirus-Specific T-Cell Therapy, for the Prevention of Viral Infections Post-HCT: Results from an Open-Label Cohort of a Phase 2 Trial. Blood. 2021; 138(Supplement 1): 1760.
- Pfeiffer T, Tzannou I, Wu M, et al. Posoleucel, an allogeneic, off-the-shelf multivirus-specific T-cell therapy, for the treatment of refractory viral infections in the post-HCT setting. Clin Cancer Res. 2023; 29(2): 324–330.
- Walti CS, Khanna N, Avery RK, et al. New treatment options for refractory/resistant CMV infection. Transpl Int. 2023; 36: 11785.
- Brestrich G, Zwinger S, Fischer A, et al. Adoptive T-cell therapy of a lung transplanted patient with severe CMV disease and resistance to antiviral therapy. Am J Transplant. 2009; 9(7): 1679–1684.
- Rubinstein JD, Jodele S, Heyenbruch D, et al. Off-the-shelf third-party virus-specific T cell therapy to treat JC polyomavirus infection in hematopoietic stem cell transplantation recipients. Transplant Cell Ther. 2022; 28(2): 116.e1–116.e7.
- Kim N, Nam YS, Im KI, et al. Robust production of cytomegalovirus pp65-specific T cells using a fully automated IFN-γ cytokine capture system. Transfus Med Hemother. 2018; 45(1): 13–22.
- Gerdemann U, Vera JF, Rooney CM, et al. Generation of multivirus-specific T cells to prevent/treat viral infections after allogeneic hematopoietic stem cell transplant. J Vis Exp. 2011(51).
- Priesner C, Esser R, Tischer S, et al. Comparative analysis of clinical-scale IFN-γ-positive T-cell enrichment using partially and fully integrated platforms. Front Immunol. 2016; 7: 393.
- Feuchtinger T, Opherk K, Bethge WA, 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(20): 4360–4367.
- Icheva V, Kayser S, Wolff D, et al. Adoptive transfer of Epstein-Barr virus (EBV) nuclear antigen 1-specific T cells as treatment for EBV reactivation and lymphoproliferative disorders after allogeneic stem-cell transplantation. J Clin Oncol. 2013; 31(1): 39–48.
- Pei XY, Zhao XY, Chang YJ, et al. Cytomegalovirus-specific T-cell transfer for refractory cytomegalovirus infection after haploidentical stem cell transplantation: The quantitative and qualitative immune recovery for cytomegalovirus. J Infect Dis. 2017; 216(8): 945–956.
- Heinz AT, Calkoen FGJ, Derbich A, et al. Automated production of specific T cells for treatment of refractory viral infections after allogeneic stem cell transplantation. Haematologica. 2023; 108(8): 2080–2090.