Clinical Use of the Interferon Inducer IIBI in Patients with Refractory Hodgkin’s Lymphoma

Daniar R. Aspetov¹ Maria N. Omarova¹; Lyazzat Zh. Orakbay¹; Raiymkul K. Karakulov²; Kairat S. Doskhozhayev²; Bayan Kh. Zhumatova¹; Meruyert D. Chazhayeva¹

¹Scientific Centre of Hygiene and Epidemiology; ²Kazakh Research Institute of Oncology and Radiology; Almaty, Kazakhstan

*Corresponding author: Lyazat Orakbay, PhD, ScD. Scientific Centre of Hygiene and Epidemiology named after Hamza Zhumatov. Almaty, Kazakhstan. E-mail: ncgigieny@mail.ru

Published: December 3, 2015. DOI: 10.21103/Article5(4)_OA9

Abstract: 

This study evaluated the effects of the immunobiological preparation "Interferon inducer bacterial liquid" (IIBI) combined with chemoradiotherapy (CRT) in patients with refractory Hodgkin’s lymphoma (HL) are presented. The clinical application of IIBI increases the efficacy of treatment. IIBI in combination with CRT induces the production of highly active endogenous IFN-α/β, provides a marked regression of the affected lymph nodes in a short period (within 7 to 10 days) of treatment, relieves B symptoms, and increases by 2 times the length of remission in patients with refractory HL.

Keywords: 
Hodgkin’s lymphoma; chemoradiotherapy; immunotherapy, INF inducer.
References: 
  1. Evens AM, Hutchings M, Diehl V. Treatment of Hodgkin lymphoma: the past, present, and future. Nat Clin Pract Oncol  2008;5(9): 543–56.
  2. Bröckelmann PJ, Engert A. The GHSG Approach to Treating Hodgkin's Lymphoma.Curr Hematol Malig Rep. 2015 Sep; 10(3):256-65.
  3. Kroemer G, Galluzzi L. Immunotherapy of hematological cancers: PD-1 blockade for the treatment of Hodgkin's lymphoma. Oncoimmunology. 2015;4(6):e1008853.
  4. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372(4):311-9.
  5. Jahn T, Zuther M, Friedrichs B, Heuser C, Guhlke S, Abken H, Hombach AA. An IL12-IL2-antibody fusion protein targeting Hodgkin's lymphoma cells potentiates activation of NK and T cells for an anti-tumor attack. PLoS One. 2012;7(9):e44482.
  6. Küppers R, Schwering I, Bräuninger A, Rajewsky K, Hansmann ML. Biology of Hodgkin's lymphoma. Ann Oncol.2002; 13 Suppl 1: 11–18.
  7. Maggio E, van den Berg A, Diepstra A, Kluiver J, Visser L, Poppema S.  Chemokines, cytokines and their receptors in Hodgkin's lymphoma cell lines and tissues. Ann Oncol.2002; 13 Suppl 1: 52–56.
  8. Kennedy-Nasser AA, Hanley P, Bollard CM. Hodgkin disease and the role of the immune system. Pediatr Hematol Oncol. 2011; 28(3):176–86.
  9. Stein H, Bob R. Is Hodgkin lymphoma just another B-cell lymphoma? Curr Hematol Malig Rep.2009; 4(3):125–8.
  10. van den Berg A, Visser L, Poppema S. High expression of the CC chemokine TARC in Reed-Sternberg cells. A possible explanation for the characteristic T-cell infiltratein Hodgkin's lymphoma. Am J Pathol. 154(6):1685–91.
  11. Poppema S, van den Berg A. Interaction between host T cells and Reed-Sternberg cells in Hodgkin lymphomas. Semin Cancer Biol.2000; 10(5):345–50.
  12. Skinnider BF, Elia AJ, Gascoyne RD, Patterson B, Trumper L, Kapp U, et al. (2002) Signal transducer and activator of transcription 6 is frequently activated in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. Blood.2002; 99(2):618–26.
  13. Dunn GP, Bruce AT, Sheehan KC, Shankaran V, Uppaluri R, Bui JD, et al. A critical function for type I interferons in cancer immunoediting. Nat Immunol. 2005; 6(7):722-9.
  14. Ferrantini M, Capone I, Belardelli F. Biochimie. Interferon-alpha and cancer: mechanisms of action and new perspectives of clinical use. Biochimie 2007; 89(6-7):884-93.
  15. Dunn GP1, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002; 3(11):991-8.
  16. Swann JB, Hayakawa Y, Zerafa N, Sheehan KC, Scott B, Schreiber RD, et al. Type I IFN contributes to NK cell homeostasis, activation, and antitumor function. J Immunol 2007;178(12):7540-9.
  17. Hasan UA, Caux C, Perrot I, Doffin AC, Menetrier-Caux C, Trinchieri G, et al. Cell proliferation and survival induced by Toll-like receptors is antagonized by type I IFNs. Proc Natl Acad Sci USA. 2007; 104(19):8047-52.
  18. Shmulevitz M, Pan LZ, Garant K, Pan D, Lee PW. Oncogenic Ras promotes reovirus spread by suppressing IFN-beta production through negative regulation of RIG-I signaling. Cancer Res. 2010;70(12):4912-21.
  19. Zitvogel L, Galluzzi L, Kepp O, Smyth MJ, Kroemer G. Type I interferons in anticancer immunity. Nat Rev Immunol. 2015; 15(7):405-14.
  20. Decker T, Müller M, Stockinger S. The yin and yang of type I interferon activity in bacterial infection. Nat Rev Immunol. 2005 Sep;5(9):675-87.
  21. Gomes MT, Campos PC, de Almeida LA, Oliveira FS, Costa MM, Marim FM, et al. The role of innate immune signals in immunity to Brucella abortus. Front Cell Infect Microbiol. 2012;2:130.
  22. Nagarajan UM, Sikes J, Prantner D, Andrews CW Jr, Frazer L, Goodwin A, et al. MyD88 deficiency leads to decreased NK cell gamma interferon production and T cell recruitment during Chlamydia muridarum genital tract infection, but a predominant Th1 response and enhanced monocytic inflammation are associated with infection resolution. Infect Immun. 2011;79(1):486-98.
  23. Monroe KM, McWhirter SM, Vance RE. Induction of type I interferons by bacteria. Cell Microbiol. 2010;12(7):881-90.
  24. Petropoulos D, Worth LL, Mullen CA, Lockhart S, Choroszy M, Chan KW. Interferon-alpha after autologous stem cell transplantation in pediatric patients with advanced Hodgkin's lymphoma. Bone Marrow Transplant. 2006;38(5):345-9.
  25. Batty N, Hagemeister FB, Feng L, Romaguera JE, Rodriguez MA, McLaughlin P, et al. Doxorubicin, bleomycin, vinblastine and dacarbazine chemotherapy with interferon for advanced stage classic Hodgkin lymphoma: a 10-year follow-up study. Leuk Lymphoma. 2012;53(5):801-6.
  26. Isaacs A, Lindenmann J.  Pillars Article: Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci. 1957;147;258–267
  27. Meissner NN, Swain S, Tighe M, Harmsen A, Harmsen A. Role of type I IFNs in pulmonary complications of Pneumocystis murina infection. J Immunol. 2005;174(9): 5462–71.
  28. Monroe KM, McWhirter SM, Vance RE.  Induction of type I interferons by bacteria. Cell Microbiol. 2010;12(7): 881–90.
  29. Sharma S, Deoliveira RB, Kalantari P, Parroche P, Goutagny N, Jiang Z, et al. Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome. Immunity. 2011;35(2):194–207.
  30. de La Maza LM, Peterson EM, Goebel JM, Fennie CW, Czarniecki CW.  Interferon-induced inhibition of Chlamydia trachomatis: dissociation from antiviral and antiproliferative effects. Infect Immun. 1985;47(3):719–22.
  31. Buss C, Opitz B, Hocke AC, Lippmann J, Van Laak V, Hippenstiel S, et al. Essential role of mitochondrial antiviral signaling, IFN regulatory factor (IRF)3, and IRF7 in Chlamydophila pneumoniae-mediated IFN-beta response and control of bacterial replication in human endothelial cells. J Immunol. 2010;184(6): 3072–8.
  32. Plumlee CR, Lee C, Beg AA, Decker T, Shuman HA, Schindler C.  Interferons direct an effective innate response to Legionella pneumophila infection. J Biol Chem. 2009;284(44):30058–66.
  33. Carrero JA, Calderon B, Unanue ER. Lymphocytes are detrimental during the early innate immune response against Listeria monocytogenes. J Exp Med. 2006;203(4): 933–40.
  34. O'Connell RM, Saha SK, Vaidya SA, Bruhn KW, Miranda GA, Zarnegar B, et al. Type I interferon production enhances susceptibility to Listeria monocytogenes infection. J Exp Med. 2004;200(4):437–45.
  35. Qiu H, Fan Y, Joyee AG, Wang S, Han X, Bai H, et al. Type I IFNs enhance susceptibility to Chlamydia muridarum lung infection by enhancing apoptosis of local macrophages. J Immunol. 2008;181(3): 2092–102.
  36. Huang LY, Ishii KJ, Akira S, Aliberti J, Golding B. Th1-like cytokine induction by heat-killed Brucella abortus is dependent on triggering of TLR9. J Immunol. 2005; 175(6):3964–70.
  37. Salcedo SP, Marchesini MI, Lelouard H, Fugier E, Jolly G, Balor S, et al. Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btp1. PLoS Pathog. 2008;4(2):e21.
  38. Interferon inducer bacterial liquid.State Register of medicinal products of the Republic of Kazakhstan.  2012; IDA  42-33-68-11.
  39. Jaffe ES. The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Hematology Am Soc Hematol Educ Program. 2009. 523-31.
  40. Kovrigina AM, Probatova NA. Morphoimmunohistological differential diagnosis between Hodgkin's lymphoma with lymphoid prevalence and large B-cell lymphoma. Arkh Patol. 2005; 67(4):10-6 [Article in Russian].
  41. Novokhatskiĭ AS, Cherkashina NP, Ershov FI. Accelerated method of determining the antiviral activity of interferon inducers in experimental infection. Vopr Virusol. 1979;3:303-6. [Article in Russian].

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