CMV-specific T cells generated from naïve T cells recognize atypical epitopes and may be protective in vivo

Science Translational Medicine

Volumn 7, Issue 285, 2015, Pages

  Hanley, Patrick J ^a,b,c   Melenhorst, Jan J ^d   Nikiforow, Sarah ^e   Scheinberg, Phillip ^d   Blaney, James W ^a   Demmler Harrison, Gail ^b   Cruz, C Russell ^a,c   Lam, Sharon ^a,b,c   Krance, Robert A ^a,b   Leung, Kathryn S ^a,b   Martinez, Caridad A ^a,b   Liu, Hao ^a   Douek, Daniel C ^f   Heslop, Helen E ^a,b   Rooney, Cliona M ^a,b   Shpall, Elizabeth J ^g   Barrett, A John ^d   Bollard, Catherine M ^a,b,c  

^a HOUSTON METHODIST HOSPITAL   (United States)

^b BAYLOR COLLEGE OF MEDICINE   (United States)

^c GEORGE WASHINGTON UNIVERSITY   (United States)

^d NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

^e HARVARD MEDICAL SCHOOL   (United States)

^f NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^g UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATYPICAL EPITOPE; CD16 ANTIGEN; CD3 ANTIGEN; CD40 LIGAND; CD45RA ANTIGEN; CD56 ANTIGEN; CHEMOKINE RECEPTOR CCR7; CYTOMEGALOVIRUS ANTIGEN PP65; EPITOPE; FOSCARNET; GAMMA INTERFERON; GANCICLOVIR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HLA A2 ANTIGEN; INTERLEUKIN 2; T LYMPHOCYTE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; LYMPHOCYTE ANTIGEN RECEPTOR;

ACUTE LYMPHOBLASTIC LEUKEMIA; ARTICLE; CASE REPORT; CD8+ T LYMPHOCYTE; CELL EXPANSION; CELL STIMULATION; CELL THERAPY; CHILD; CORD BLOOD GRAFT; CORD BLOOD STEM CELL TRANSPLANTATION; CYTOMEGALOVIRUS INFECTION; CYTOMEGALOVIRUS SPECIFIC T LYMPHOCYTE; DENDRITIC CELL; DRUG SAFETY; ENZYME LINKED IMMUNOSPOT ASSAY; FANCONI ANEMIA; FEASIBILITY STUDY; FLOW CYTOMETRY; GRAFT RECIPIENT; HIGH RISK POPULATION; HUMAN; HUMAN CELL; IMMUNOPROPHYLAXIS; IMMUNOSUPPRESSIVE TREATMENT; IN VIVO STUDY; INFECTION PREVENTION; LIMIT OF DETECTION; MALE; MEMORY T LYMPHOCYTE; NATURAL KILLER CELL; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PRESCHOOL CHILD; PRIORITY JOURNAL; REMISSION; SEVERE COMBINED IMMUNODEFICIENCY; T LYMPHOCYTE; TISSUE GRAFT; VIRUS LOAD; CYTOMEGALOVIRUS; IMMUNOLOGY; PHYSIOLOGY; VIROLOGY;

CYTOMEGALOVIRUS; EPITOPES; HUMANS; RECEPTORS, ANTIGEN, T-CELL; T-LYMPHOCYTES;

EID: 84929493070     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aaa2546     Document Type: Article

References (50)

1. A. M. Leen, G. D. Myers, U. Sili, M. H. Huls, H. Weiss, K. S. Leung, G. Carrum, R. A. Krance, C C Chang, J. J. Molldrem, A. P. Gee, M. K. Brenner, H. E. Heslop, C. M. Rooney, C. M. Bollard, Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals. Nat. Med. 12, 1160-1166 (2006).
2. A. M. Leen, A. Christin, G. D. Myers, H. Liu, C R. Cruz, P. J. Hanley, A. A. Kennedy-Nasser, K. S. Leung, A. P. Gee, R. A. Krance, M. K. Brenner, H. E. Heslop, C. M. Rooney, C. M. Bollard, 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 114,4283-4292 (2009).
3. K. P. Micklethwaite, L. Clancy, U. Sandher, A. M. Hansen, E. Blyth, V. Antonenas, M. M. Sartor, K. F. Bradstock, D. J. Gottlieb, Prophylactic infusion of cytomegalovirus-specific cytotoxic T lymphocytes stimulated with Ad5f35pp65 gene-modified dendritic cells after allogeneic hemopoietic stem cell transplantation. Blood 112, 3974-3981 (2008).
4. K. S. Peggs, K. Thomson, E. Samuel, G. Dyer, J. Armoogum, R. Chakraverty, K. Pang, S. Mackinnon, M. W. Lowdell, Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation. Clin. Infect. Dis. 52,49-57 (2011).
5. E. A. Walter, P. D. Greenberg, M. J. Gilbert, R. J. Finch, K. S. Watanabe, E. D. Thomas, S. R. Riddell, 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. 333, 1038-1044 (1995).
6. C. R. Cruz, K. P. Micklethwaite, B. Savoldo, C. A. Ramos, S. Lam, S. Ku, O. Diouf, E. Liu, A. J. Barrett, S. Ito, E. J. Shpall, R. A. Krance, R. T. Kamble, G. Carrum, C. M. Hosing, A. P. Gee, Z. Mei, B. J. Grilley, H. E. Heslop, C. M. Rooney, M. K. Brenner, C. M. Bollard, G. Dotti, 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, 2965-2973 (2013).
7. S. A. Grupp, M. Kalos, D. Barrett, R. Aplenc, D. L. Porter, S. R. Rheingold, D. T. Teachey, A. Chew, B. Hauck, J. F.Wright, M. C. Milone, B. L. Levine, C. H.June, Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N. Engl. J. Med. 368, 1509-1518 (2013).
8. J. N. Kochenderfer, M. E. Dudley, R. O. Carpenter, S. H. Kassim, J. J. Rose, W. G. Telford, F. T. Hakim, D. C. Halverson, D. H. Fowler, N. M. Hardy, A. R. Mato, D. D. Hickstein, J. C. Gea-Banacloche, S. Z. Pavletic, C. Sportes, I. Marie, S. A. Feldman, B. G. Hansen, J. S. Wilder, B. Blacklock-Schuver, B. Jena, M. R. Bishop, R. E. Gress, S. A. Rosenberg, Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood 122,4129-4139 (2013).
9. M. K. Brenner, H. E. Heslop, Adoptive T cell therapy of cancer. Curr. Opin. Immunol. 22,251-257 (2010) .
10. S. A. Pergam, H. Xie, R. Sandhu, M. Pollack, J. Smith, T. Stevens-Ayers, V. Ilieva, L. E. Kimball, M. L. Huang, T. S. Hayes, L. Corey, M. J. Boeckh, Efficiency and risk factors for CMV transmission in seronegative hematopoietic stem cell recipients. Biol. Blood Marrow Transplant. 18, 1391-1400 (2012).
11. P. J. Hanley, C. R. Cruz, E. J. Shpall, C. M. Bollard, Improving clinical outcomes using adoptively transferred immune cells from umbilical cord blood. Cytotherapy 12, 713-720 (2010).
12. P. J. Hanley, C. R. Cruz, B. Savoldo, A. M. Leen, M. Stanojevic, M. Khalil, W. Decker, J. J. Molldrem, H. Liu, A. P. Gee, C. M. Rooney, H. E. Heslop, G. Dotti, M. K. Brenner, E. J. Shpall, C. M. Bollard, Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes. Blood 114, 1958-1967 (2009).
13. B. Savoldo, M. L. Cubbage, A. G. Durett, J. Goss, M. H. Huls, Z. Liu, L. Teresita, A. P. Gee, P. D. Ling, M. K. Brenner, H. E. Heslop, C. M. Rooney, Generation of EBV-specific CD4+ cytotoxic T cells from virus naive individuals. J. Immunol. 168, 909-918 (2002).
14. C S. Hinrichs, Z. A. Borman, L. Gattinoni, Z. Yu, W. R. Burns, J. Huang, C. A. Klebanoff, L A. Johnson, S. P. Kerkar, S. Yang, P. Muranski, D. C. Palmer, C. D. Scott, R. A. Morgan, P. F. Robbins, S. A. Rosenberg, N. P. Restifo, Human effector CD8+ T cells derived from naive rather than memory subsets possess superior traits for adoptive immunotherapy. Blood 117, 808-814 (2011) .
15. L. K. Borysiewicz, J. K. Hickling, S. Graham, J. Sinclair, M. P. Cranage, G. L. Smith, J. G. Sissons, Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses. J. Exp. Med. 168, 919-931 (1988).
16. M. R. Wills, A. J. Carmichael, K. Mynard, X. Jin, M. P. Weekes, B. Plachter, J. G. Sissons, The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein pp65: Frequency, specificity, and T-cell receptor usage of pp65-specific CTL. J. Virol. 70, 7569-7579 (1996).
17. E. McLaughlin-Taylor, H. Pande, S. J. Forman, B. Tanamachi, C R. Li, J. A. Zaia, P. D. Greenberg, S. R. Riddell, Identification of the major late human cytomegalovirus matrix protein pp65 as a target antigen for CD8+ virus-specific cytotoxic T lymphocytes. J. Med. Virol. 43, 103-110 (1994).
18. F. Kern, N. Faulhaber, C. Frommel, E. Khatamzas, S. Prosch, C. Schonemann, I. Kretzschmar, R. Volkmer-Engert, H. D. Volk, P. Reinke, Analysis of CD8 T cell reactivity to cytomegalovirus using protein-spanning pools of overlapping pentadecapeptides. Eur. J. Immunol. 30, 1676-1682 (2000).
19. R. Elkington, S. Walker, T. Crough, M. Menzies, J. Tellam, M. Bharadwaj, R. Khanna, Ex vivo profiling of CD8+-T-cell responses to human cytomegalovirus reveals broad and multispecific reactivities in healthy virus carriers. J. Virol. 77, 5226-5240 (2003).
20. A. W. Sylwester, B. L. Mitchell, J. B. Edgar, C Taormina, C Pelte, F. Ruchti, P. R. Sleath, K. H. Grabstein, N. A. Hosken, F. Kern, J. A. Nelson, L J. Picker, Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J. Exp. Med. 202, 673-685 (2005).
21. R. Holtappels, C. O. Simon, M. W. Munks, D.Thomas, P. Deegen, B. Kuhnapfel, T. Daubner, S. F. Emde, J. Podlech, N. K. Grzimek, S. A. Oehrlein-Karpi, A. B. Hill, M. J. Reddehase, Subdominant CD8 T-cell epitopes account for protection against cytomegalovirus independent of immunodomination. J. Virol. 82, 5781-5796 (2008).
22. R. Kaul, T. Dong, F. A. Plummer, J. Kimani, T. Rostron, P. Kiama, E. Njagi, E. Irungu, B. Farah, J. Oyugi, R. Chakraborty, K. S. MacDonald, J. J. Bwayo, A. McMichael, S. L. Rowland-Jones, CD8+ lymphocytes respond to different HIV epitopes in seronegative and infected subjects. J. Clin. Invest. 107, 1303-1310 (2001).
23. P. J. Hanley, S. Lam, E. J. Shpall, C. M. Bollard, Expanding cytotoxic T lymphocytes from umbilical cord blood that target cytomegalovirus, Epstein-Barr virus, and adenovirus. J. Vis. Exp., e3627 (2012).
24. P. J. Hanley, D. R. Shaffer, C. R. Cruz, S. Ku, B. Tzou, H. Liu, G. Demmler-Harrison, H. E. Heslop, C. M. Rooney, S. Gottschalk, C. M. Bollard, Expansion of T cells targeting multiple antigens of cytomegalovirus, Epstein-Barr virus and adenovirus to provide broad antiviral specificity after stem cell transplantation. Cytotherapy 13, 976-986 (2011).
25. G. Badr, N. Bedard, M. S. Abd el -Hakeem, L.Trautmann, B. Willems, J. P. Villeneuve, E. K. Haddad, R. P. Sekaly, J. Bruneau, N. H. Shoukry, Early interferon therapy for hepatitis C virus infection rescues polyfunction a I, long-lived CD8+ memory T cells. J. Virol. 82, 10017-10031 (2008).
26. S. Kannanganat, C. Ibegbu, L. Chennareddi, H. L. Robinson, R. R. Amara, Multiple-cytokine-producing antiviral CD4 T cells are functionally superior to single-cytokine-producing cells. J. Virol. 81, 8468-8476 (2007).
27. U. Gerdemann, J. M. Keirnan, U. L. Katari, R. Yanagisawa, A. S. Christin, L. E. Huye, S. K. Perna, S. Ennamuri, S. Gottschalk, M. K. Brenner, H. E. Heslop, C. M. Rooney, A. M. Leen, Rapidly generated multivirus-specific cytotoxic T lymphocytes for the prophylaxis and treatment of viral infections. Moi. Ther. 20, 1622-1632 (2012).
28. K. Micklethwaite, A. Hansen, A. Foster, E. Snape, V. Antonenas, M. Sartor, P. Shaw, K. Bradstock, D. Gottlieb, Ex vivo expansion and prophylactic infusion of CMV-pp65 peptide-specific cytotoxic T-lymphocytes following allogeneic hematopoietic stem cell transplantation. Biol. Blood Marrow Transplant. 13, 707-714 (2007).
29. G. Aubert, A. F. Hassan-Walker, J. A. Madrigal, V. C. Emery, C. Morte, S. Grace, M. B. Koh, M. Potter, H. G. Prentice, I. A. Dodi, P. J. Travers, Cytomegalovirus-specific cellular immune responses and viremia in recipients of allogeneic stem cell transplants. J. Infect. Dis. 184, 955-963 (2001).
30. I. Jedema, M. van de Meent, J. Pots, M. G. Kester, M. T. van der Beek, J. H. Falkenburg, Successful generation of primary virus-specific and anti-tumor T-cell responses from the naive donor T-cell repertoire is determined by the balance between antigen-specific precursor T cells and regulatory T cells. Haematologica 96, 1204-1212 (2011).
31. J. W.Gratama, J.W. van Esser, C. H. Lamers, CTournay, B. Lowenberg, R. L. Bolhuis, J. J.Cornelissen, Tetramer-based quantification of cytomegalovirus (CMV)-specific CD8+ T lymphocytes in T-cell-depleted stem cell grafts and after transplantation may identify patients at risk for progressive CMV infection. Blood 98, 1358-1364 (2001).
32. M. G. Revello, G. Gerna, Human cytomegalovirus tropism for endothelial/epithelial cells: Scientific background and clinical implications. Rev. Med. Virol. 20, 136-155 (2010).
33. A. Loewendorf, C. A. Benedict, Modulation of host innate and adaptive immune defenses by cytomegalovirus: Timing is everything. J. Intern. Med. 267, 483-501 (2010).
34. C. A. Benedict, A. Loewendorf, Z. Garcia, B. R. Blazar, E. M. Janssen, Dendritic cell programming by cytomegalovirus stunts naive T cell responses via the PD-L1/PD-1 pathway. J. Immunol. 180, 4836-4847 (2008).
35. M. Altfeld, E. S. Rosenberg, R. Shankarappa, J. S. Mukherjee, F. M. Hecht, R. L. Eldridge, M. M. Addo, S. H. Poon, M. N. Phillips, G. K. Robbins, P. E. Sax, S. Boswell, J. O. Kahn, C. Brander, P. J. Goulder, J. A. Levy, J. I. Mullins, B. D. Walker, Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J. Exp. Med. 193, 169-180 (2001).
36. P. J. Goulder, M. A. Altfeld, E. S. Rosenberg, T. Nguyen, Y. Tang, R. L. Eldridge, M. M. Addo, S. He, J. S. Mukherjee, M. N. Phillips, M. Bunce, S. A. Kalams, R. P. Sekaly, B. D. Walker, C. Brander, Substantial differences in specificity of HlV-specific cytotoxic T cells in acute and chronic HIV infection. J. Exp. Med. 193, 181-194 (2001).
37. A. D. Hislop, N. E. Annels, N. H. Gudgeon, A. M. Leese, A. B. Rickinson, Epitope-specific evolution of human CD8+ T cell responses from primary to persistent phases of Epstein-Barr virus infection. J. Exp. Med. 195, 893-905 (2002).
38. M. Bharadwaj, S. R. Burrows, J. M. Burrows, D. J. Moss, M. Catalina, R. Khanna, Longitudinal dynamics of antigen-specific CD8+ cytotoxic T lymphocytes following primary Epstein-Barr virus infection. Blood 98, 2588-2589 (2001).
39. S. G. Hansen, J. B. Sacha, C. M. Hughes, J. C. Ford, B. J. Burwitz, I. Scholz, R. M. Gilbride, M. S. Lewis, A. N. Gilliam, A. B. Ventura, D. Malouli, G. Xu, R. Richards, N. Whizin, J. S. Reed, K. B. Hammond, M. Fischer, J. M. Turner, A. W. Legasse, M. K. Axthelm, P. T. Edlefsen, J. A. Nelson, J. D. Lifson, K. Fruh, L. J. Picker, Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science 340, 1237874 (2013).
40. C. Berger, M. C. Jensen, P. M. Lansdorp, M. Gough, C. Elliott, S. R. Riddell, Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. J. Clin. Invest. 118, 294-305 (2008).
41. C. S. Hinrichs, Z. A. Borman, L. Cassard, L. Gattinoni, R. Spolski, Z. Yu, L. Sanchez-Perez, P. Muranski, S. J. Kern, C. Logun, D. C. Palmer, Y. Ji, R. N. Reger, W. J. Leonard, R. L. Danner, S. A. Rosenberg, N. P. Restifo, Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity. Proc. Natl. Acad. Sci. USA. 106, 17469-17474 (2009).
42. M. Cobbold, N. Khan, B. Pourgheysari, S. Tauro, D. McDonald, H. Osman, M. Assenmacher, L. Billingham, C. Steward, C. Crawley, E. Olavarria, J. Goldman, R. Chakraverty, P. Mahendra, C. Craddock, P. A. Moss, Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers. J. Exp. Med. 202, 379-386 (2005).
43. F. Saglio, P. J. Hanley, C. M. Bollard, The time is now: Moving toward virus-specific T cells after allogeneic hematopoietic stem cell transplantation as the standard of care. Cytotherapy 16, 149-159 (2014).
44. A. M. Leen, C. M. Bollard, A. M. Mendizabal, E. J. Shpall, P. Szabolcs, J. H. Antin, N. Kapoor, S. Y. Pai, S. D. Rowley, P. Kebriaei, B. R. Dey, B. J. Grilley, A. P. Gee, M. K. Brenner, C. M. Rooney, H. E. Heslop, Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood 121, 5113-5123 (2013).
45. J. N. Barker, E. Doubrovina, C. Sauter, J. J. Jaroscak, M. A. Perales, M. Doubrovin, S. E. Prockop, G. Koehne, R. J. O'Reilly, Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes. Blood 116, 5045-5049 (2010).
46. M. Uhlin, M. Okas, J. Gertow, M. Uzunel, T. B. Brismar, J. Mattsson, A novel haplo-identical adoptive CTL therapy as a treatment for EBV-associated lymphoma after stem cell transplantation. Cancer Immunol. Immunother. 59, 473-477 (2010).
47. W. Qasim, S. Derniame, K. Gilmour, R. Chiesa, M. Weber, S. Adams, K. Rao, P. Amrolia, N. Goulden, P. Veys, H. Gaspar, Third-party virus-specific T cells eradicate adenoviraemia but trigger bystander graft-versus-host disease. Br. J. Haematol. 154, 150-153 (2011).
48. E. M. Sloand, J. J. Melenhorst, Z. C. Tucker, L. Pfannes, J. M. Brenchley, A. Yong, V. Visconte, C. Wu, E. Gostick, P. Scheinberg, M. J. Olnes, D. C. Douek, D. A. Price, A. J. Barrett, N. S. Young, T-cell immune responses to Wilms tumor 1 protein in myelodysplasia responsive to immunosuppressive therapy. Blood 117, 2691-2699 (2011).
49. J. J. Melenhorst, P. Castillo, P. J. Hanley, M. D. Keller, R. A. Krance, J. Margolin, A. M. Leen, H. E. Heslop, A. J. Barrett, C. M. Rooney, C. M. Bollard, Graft versus leukemia response without graft-versus-host disease elicited by adoptively transferred multivirus-specific T-cells. Mol. Ther. 23, 179-183 (2015).
50. C. Cutler, P. Multani, D. Robbins, H. T. Kim, T. Le, J. Hoggatt, L. M. Pelus, C. Desponts, Y. B. Chen, B. Rezner, P. Armand, J. Koreth, B. Glotzbecker, V. T. Ho, E. Alyea, M. Isom, G. Kao, M. Armant, L. Silberstein, P. Hu, R. J. Soiffer, D. T. Scadden, J. Ritz, W. Goessling, T. E. North, J. Mendlein, K. Ballen, L. I. Zon, J. H. Antin, D. D. Shoemaker, Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. Blood 122, 3074-3081 (2013).