Ultra low-dose IL-2 for GVHD prophylaxis after allogeneic hematopoietic stem cell transplantation mediates expansion of regulatory t cells without diminishing antiviral and antileukemic activity

Clinical Cancer Research

Volumn 20, Issue 8, 2014, Pages 2215-2225

  Kennedy Nasser, Alana A ^a   Ku, Stephanie ^a   Castillo Caro, Paul ^a   Hazrat, Yasmin ^a   Wu, Meng Fen ^b   Liu, Hao ^b   Melenhorst, Jos ^d   Barrett, A John ^d   Ito, Sawa ^d   Foster, Aaron ^a   Savoldo, Barbara ^a   Yvon, Eric ^a   Carrum, George ^a,c   Ramos, Carlos A ^a,c   Krance, Robert A ^a,c   Leung, Kathryn ^a   Heslop, Helen E ^a,c   Brenner, Malcolm K ^a,c   Bollard, Catherine M ^a,c  

^a CENTER FOR CELL AND GENE THERAPY   (United States)

^b BAYLOR COLLEGE OF MEDICINE   (United States)

^c HOUSTON METHODIST HOSPITAL   (United States)

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

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; INTERLEUKIN 2 RECEPTOR ALPHA; RECOMBINANT INTERLEUKIN 2; TRANSCRIPTION FACTOR FOXP3; ANTIVIRUS AGENT; INTERLEUKIN 2;

ACUTE GRAFT VERSUS HOST DISEASE; ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ADOLESCENT; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; ARTHRALGIA; ARTICLE; CD4+ CD25+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL EXPANSION; CELLULAR IMMUNITY; CHILD; CLINICAL ARTICLE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DECREASED APPETITE; DOSE RESPONSE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FEMALE; HUMAN; HUMORAL IMMUNITY; IMMUNOPROPHYLAXIS; INFECTION RATE; LOW DRUG DOSE; MALE; MYALGIA; NATURAL KILLER CELL; NAUSEA; NONHODGKIN LYMPHOMA; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROSPECTIVE STUDY; REGULATORY T LYMPHOCYTE; SCHOOL CHILD; UNSPECIFIED SIDE EFFECT; VIRUS INFECTION; ALLOTRANSPLANTATION; BLOOD; CELL PROLIFERATION; CLINICAL TRIAL; CYTOLOGY; DRUG EFFECTS; FLOW CYTOMETRY; GRAFT VS HOST DISEASE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; LEUKEMIA; LYMPHOCYTE COUNT; TREATMENT OUTCOME;

ADOLESCENT; ANTIVIRAL AGENTS; CELL PROLIFERATION; CHILD; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; FLOW CYTOMETRY; GRAFT VS HOST DISEASE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; INTERLEUKIN-2; LEUKEMIA; LYMPHOCYTE COUNT; MALE; PROSPECTIVE STUDIES; T-LYMPHOCYTES, REGULATORY; TRANSPLANTATION, HOMOLOGOUS; TREATMENT OUTCOME;

EID: 84898940914     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-13-3205     Document Type: Article

References (39)

1. Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet 2009;373:1550-61.
2. Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb H-J, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990;75:555-62.
3. Negrin RS. Role of regulatory T cell populations in controlling graft vs host disease. Best Pract Res Clin Haematol 2011;24:453-7.
4. Nguyen VH, Shashidhar S, Chang DS, Ho L, Kambham N, Bachmann M, et al. The impact of regulatory T cells on T-cell immunity following hematopoietic cell transplantation. Blood 2008;111:945-53.
5. Zeiser R, Nguyen VH, Beilhack A, Buess M, Schulz S, Baker J, et al. Inhibition of CD4+CD25+ regulatory T-cell function by calcineurindependent interleukin-2 production. Blood 2006;108:390-9.
6. Asano MS, Ahmed R. CD8 T cellmemory in B cell-deficient mice. J Exp Medicine 1996;183:2165-74.
7. Malek TR, Bayer AL. Tolerance, not immunity, crucially depends on IL- 2. Nat Rev Immunol 2004;4:665-74.
8. Kennedy-Nasser AA, Bollard CM, Myers GD, Leung KS, Gottschalk S, Zhang Y, et al. Comparable outcome of alternative donor and matched sibling donor hematopoietic stem cell transplant for children with acute lymphoblastic leukemia in first or second remission using alemtuzumab in a myeloablative conditioning regimen. Biol Blood Marrow Transplant 2008;14:1245-52.
9. Ahmed N, Leung KS, Rosenblatt H, Bollard CM, Gottschalk S, Myers GD, et al. Successful treatment of stem cell graft failure in pediatric patients using a submyeloablative regimen of campath-1H and fludarabine. Biol Blood Marrow Transplant 2008;14:1298-304.
10. Leen AM, Myers GD, Sili U, Huls MH, Weiss H, Leung KS, et al. Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals. Nat Med 2006;12:1160-6.
11. Weber G, Gerdemann U, Caruana I, Savoldo B, Hensel NF, Rabin KR, et al. Generation of multi-leukemia antigen-specific T cells to enhance the graft-versus-leukemia effect after allogeneic stem cell transplant. Leukemia 2013;27:1538-47.
12. Weber G, Caruana I, Rouce RH, Barrett J, Leen AM, Rabin KR, et al. Generation of tumor antigen-specific T cell lines from pediatric patients with acute lymphoblastic leukemia - implications for immunotherapy. Clin Cancer Res 2013;19:5079-91.
13. Bryant J, Day R. Incorporating toxicity considerations into the design of two-stage phase II clinical trials. Biometrics 1995;51:1372-83.
14. Cesana GC, DeRaffele G, Cohen S, Moroziewicz D, Mitcham J, Stoutenburg J, et al. Characterization of CD4+CD25+ regulatory T cells in patients treated with high-dose interleukin-2 for metastatic melanoma or renal cell carcinoma. J Clin Oncol 2006;24:1169-77.
15. Shah MH, Freud AG, Benson DM Jr, Ferkitich AK, Dezube BJ, Bernstein ZP, et al. A phase I study of ultra low dose interleukin-2 and stem cell factor in patients with HIV infection or HIV and cancer. Clin Cancer Res 2006;12:3993-6.
16. Zhang H, Chua KS, Guimond M, Kapoor V, Brown MV, Fleisher TA, et al. Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat Med 2005;11:1238-43.
17. Soiffer RJ, Murray C, Cochran K, Cameron C, Wang E, Schow PW, et al. Clinical and immunologic effects of prolonged infusion of low-dose recombinant interleukin-2 after autologous and T-celldepleted allogeneic bone marrow transplantation. Blood 1992;79: 517-26.
18. Soiffer RJ, Murray C, Gonin R, Ritz J. Effect of low-dose interleukin-2 on disease relapse after T-cell-depleted allogeneic bone marrow transplantation. Blood 1994;84:964-71.
19. Zorn E, Nelson EA, Mohseni M, Porcheray F, Kim H, Litsa D, et al. IL-2 regulates FOXP3 expression in human CD4+CD25+regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood 2006;108:1571-9.
20. Gottlieb DJ, Prentice HG, Heslop HE, Bello-Fernandez C, Bianchi AC, Galazka AR, et al. Effects of recombinant interleukin-2 administration on cytotoxic function following high-dose chemo- radiotherapy for hematological malignancy. Blood 1989;74: 2335-42.
21. Gottlieb DJ, Brenner MK, Heslop HE, Bianchi AC, Bello-Fernandez C, Mehta AB, et al. A phase I clinical trial of recombinant interleukin 2 following high dose chemo-radiotherapy for haematological malignancy: applicability to the elimination of minimal residual disease. Br J Cancer 1989;60:610-5.
22. Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea EP III, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med 2011;365:2055-66.
23. Matsuoka K, Koreth J, Kim HT, Bascug G, McDonough S, Kawano Y, et al. Low-dose interleukin-2 therapy restores regulatory T cell homeostasis in patients with chronic graft-versus-host disease. Sci Transl Med 2013;5:179ra43.
24. Morris EC, Rebello P, Thomson KJ, Peggs KS, Kyriakou C, Goldstone AH, et al. Pharmacokinetics of alemtuzumab used for in vivo and in vitro T-cell depletion in allogeneic transplantations: relevance for early adoptive immunotherapy and infectious complications. Blood 2003; 102:404-6.
25. Rezvani K, Mielke S, Ahmadzadeh M, Kilical Y, Savani BN, Zeilah J, et al. High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT. Blood 2006;108:1291-7.
26. Di Ianni M, Falzetti F, Carotti A, Terenzi A, Del PB, Perruccio K, et al. Immunoselection and clinical use of T regulatory cells in HLA-haploidentical stem cell transplantation. Best Pract Res Clin Haematol 2011;24:459-66.
27. Hippen KL, Riley JL, June CH, Blazar BR. Clinical perspectives for regulatory T cells in transplantation tolerance. Semin Immunol 2011; 23:462-8.
28. Brunstein CG, Miller JS, Cao Q,McKenna DH, Hippen KL, Curtsinger J, et al. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood 2011;117:1061-70.
29. Thornton CA, Upham JW, Wikstrom ME, Holt BJ, White GP, Sharp MJ, et al. Functional maturation of CD4+CD25+CTLA4+CD45RA+ T regulatory cells in human neonatal T cell responses to environmental antigens/allergens. J Immunol 2004;173:3084-92.
30. Gottlieb DJ, Prentice HG, Heslop HE, Bello C, Brenner MK. IL-2 infusion abrogates humoral immune responses in humans. Clin Exp Immunol 1992;87:493-8.
31. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell 2008;133:775-87.
32. Kursar M, Bonhagen K, Fensterle J, Kohler A, Hurwitz R, Kamradt T, et al. Regulatory CD4+CD25+ T cells restrict memory CD8+ T cell responses. J Exp Med 2002;196:1585-92.
33. Rezvani K, Barrett AJ. Characterizing and optimizing immune responses to leukaemia antigens after allogeneic stem cell transplantation. Best Pract Res Clin Haematol 2008;21:437-53.
34. Molldrem JJ, Lee PP, Wang C, Felio K, Kantarjian HM, Champlin RE, et al. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med 2000;6: 1018-23.
35. Molldrem JJ, Lee PP, Wang C, Champlin RE, Davis MM. A PR1- human leukocyte antigen-A2 tetramer can be used to isolate lowfrequency cytotoxic T lymphocytes from healthy donors that selectively lyse chronic myelogenous leukemia. Cancer Res 1999;59: 2675-81.
36. Barrett J, Rezvani K. Immunotherapy: can we include vaccines with stem-cell transplantation? Nat Rev Clin Oncol 2009;6:503-5.
37. Rezvani K, Grube M, Brenchley JM, Sconocchia G, Fujiwara H, Price DA, et al. Functional leukemia-associated antigen-specific memory CD8+ T cells exist in healthy individuals and in patients with chronic myelogenous leukemia before and after stem cell transplantation. Blood 2003;102:2892-900.
38. Rezvani K, Brenchley JM, Price DA, Kilical Y, Gostick E, Sewell AK, et al. T-cell responses directed against multiple HLA-A-0201- restricted epitopes derived from Wilms' tumor 1 protein in patients with leukemia and healthy donors: identification, quantification, and characterization. Clin Cancer Res 2005;11: 8799-807.
39. Melenhorst JJ, Scheinberg P, Williams A, Ambrozak DR, Keyvanfar K, Smith M, et al. Alloreactivity across HLA barriers is mediated by both naive and antigen-experienced T cells. Biol Blood Marrow Transplant 2011;17:800-9.