DOI QR코드

DOI QR Code

Ex vivo Boosted Immune Cell Therapy for Canine Hepatic Disease

  • Bae, Seulgi (Department of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Oh, Taeho (Department of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University)
  • 투고 : 2021.03.24
  • 심사 : 2021.06.17
  • 발행 : 2021.08.31

초록

A 12-year-old male American Cocker Spaniel was diagnosed with a type of chronic hepatits (CH) called cholangioheaptits. Routine supportive medication was administered to the patient, and ex vivo boosted immune cell (EBI-C) therapy was used for the treatment. A histopathologic examination of the liver 19 months later revealed that the cholangiohepatitis had progressed to cholangiocarcinoma. The medication and immune cell therapy was maintained. Two months after the new diagnosis, the patient's state worsened, and the dog died 635 days after the first visit. EBI-C therapy is a type of immunotherapy, where immune cells are isolated from the patient's peripheral blood mononuclear cells, expanded ex vivo, and then infused into the patient intravenously every two weeks. EBI-Cs (mean: 2.78 × 108 cells) were obtained 38 times and infused every two weeks. Most EBI-C were T-lymphocytes (99.24% of total EBI cells). T-lymphocytes produce large interferon (IFN)-γ, and IFN-γ inhibits liver fibrosis in dogs with CH. Moreover, in bile duct cancer, an increase in T-lymphocytes correlates with decreasing tumor invasion and metastasis. Thus, we propose that EBI-C therapy is applicable as a new supportive therapy for canine liver disease if other treatments like drug medication, surgery, or radiation are unavailable.

키워드

과제정보

This work was financially supported by Kyungpook National University.

참고문헌

  1. Andersson M, Sevelius E. Breed, sex and age distribution in dogs with chronic liver disease: a demographic study. J Small Anim Pract 1991; 32: 1-5. https://doi.org/10.1111/j.1748-5827.1991.tb00844.x
  2. Baroni GS, D'Ambrosio L, Curto P, Casini A, Mancini R, Jezequel AM, et al. Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis. Hepatology 1996; 23: 1189-1199. https://doi.org/10.1002/hep.510230538
  3. Bexfield NH, Andres-Abdo C, Scase TJ, Constantino-Casas F, Watson PJ. Chronic hepatitis in the English springer spaniel: clinical presentation, histological description and outcome. Vet Rec 2011; 169: 415. https://doi.org/10.1136/vr.d4665
  4. Bexfield NH, Buxton RJ, Vicek TJ, Day MJ, Bailey SM, Haugland SP, et al. Breed, age and gender distribution of dogs with chronic hepatitis in the United Kingdom. Vet J 2012; 193: 124-128. https://doi.org/10.1016/j.tvjl.2011.11.024
  5. Bolkenius U, Hahn D, Gressner AM, Breitkopf K, Dooley S, Wickert L. Glucocorticoids decrease the bioavailability of TGF-beta which leads to a reduced TGF-beta signaling in hepatic stellate cells. Biochem Biophys Res Commun 2004; 325: 1264-1270. https://doi.org/10.1016/j.bbrc.2004.10.164
  6. Center SA, Warner KL, McCabe J, Foureman P, Hoffmann WE, Erb HN. Evaluation of the influence of S-adenosylmethionine on systemic and hepatic effects of prednisolone in dogs. Am J Vet Res 2005; 66: 330-341. https://doi.org/10.2460/ajvr.2005.66.330
  7. Czaja AJ, Carpenter HA. Decreased fibrosis during corticosteroid therapy of autoimmune hepatitis. J Hepatol 2004; 40: 646-652. https://doi.org/10.1016/j.jhep.2004.01.009
  8. Dill-Macky E. Chronic hepatitis in dogs. Vet Clin North Am Small Anim Pract 1995; 25: 387-398. https://doi.org/10.1016/S0195-5616(95)50033-6
  9. Favier RP. Idiopathic hepatitis and cirrhosis in dogs. Vet Clin North Am Small Anim Pract 2009; 39: 481-488. https://doi.org/10.1016/j.cvsm.2009.01.002
  10. Gatto M, Bragazzi MC, Semeraro R, Napoli C, Gentile R, Torrice A, et al. Cholangiocarcinoma: update and future perspectives. Dig Liver Dis 2010; 42: 253-260. https://doi.org/10.1016/j.dld.2009.12.008
  11. Higuchi R, Yamamoto M, Hatori T, Shimizu K, Imai K, Takasaki K. Intrahepatic cholangiocarcinoma with lymph node metastasis successfully treated by immunotherapy with CD3-activated T cells and dendritic cells after surgery: report of a case. Surg Today 2006; 36: 559-562. https://doi.org/10.1007/s00595-006-3201-1
  12. June CH. Adoptive T cell therapy for cancer in the clinic. J Clin Invest 2007; 117: 1466-1476. https://doi.org/10.1172/JCI32446
  13. Kanemoto H, Sakai M, Sakamoto Y, Spee B, van den Ingh TS, Schotanus BA, et al. American Cocker Spaniel chronic hepatitis in Japan. J Vet Intern Med 2013; 27: 1041-1048. https://doi.org/10.1111/jvim.12126
  14. Leen AM, Rooney CM, Foster AE. Improving T cell therapy for cancer. Annu Rev Immunol 2007; 25: 243-265. https://doi.org/10.1146/annurev.immunol.25.022106.141527
  15. Nakakubo Y, Miyamoto M, Cho Y, Hida Y, Oshikiri T, Suzuoki M, et al. Clinical significance of immune cell infiltration within gallbladder cancer. Br J Cancer 2003; 89: 1736-1742. https://doi.org/10.1038/sj.bjc.6601331
  16. Oshikiri T, Miyamoto M, Shichinohe T, Suzuoki M, Hiraoka K, Nakakubo Y, et al. Prognostic value of intratumoral CD8+ T lymphocyte in extrahepatic bile duct carcinoma as essential immune response. J Surg Oncol 2003; 84: 224-228. https://doi.org/10.1002/jso.10321
  17. Patel T. Cholangiocarcinoma. Nat Clin Pract Gastroenterol Hepatol 2006; 3: 33-42. https://doi.org/10.1038/ncpgasthep0389
  18. Patnaik AK, Hurvitz AI, Lieberman PH. Canine hepatic neoplasms: a clinicopathologic study. Vet Pathol 1980; 17: 553-564. https://doi.org/10.1177/030098588001700504
  19. Poldervaart JH, Favier RP, Penning LC, van den Ingh TS, Rothuizen J. Primary hepatitis in dogs: a retrospective review (2002-2006). J Vet Intern Med 2009; 23: 72-80. https://doi.org/10.1111/j.1939-1676.2008.0215.x
  20. Raffan E, McCallum A, Scase TJ, Watson PJ. Ascites is a negative prognostic indicator in chronic hepatitis in dogs. J Vet Intern Med 2009; 23: 63-66. https://doi.org/10.1111/j.1939-1676.2008.0230.x
  21. Rockey DC, Chung JJ. Interferon gamma inhibits lipocyte activation and extracellular matrix mRNA expression during experimental liver injury: implications for treatment of hepatic fibrosis. J Investig Med 1994; 42: 660-670.
  22. Rockey DC, Maher JJ, Jarnagin WR, Gabbiani G, Friedman SL. Inhibition of rat hepatic lipocyte activation in culture by interferon-gamma. Hepatology 1992; 16: 776-784. https://doi.org/10.1002/hep.1840160325
  23. Rosenberg SA, Dudley ME. Adoptive cell therapy for the treatment of patients with metastatic melanoma. Curr Opin Immunol 2009; 21: 233-240. https://doi.org/10.1016/j.coi.2009.03.002
  24. Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 2008; 8: 299-308. https://doi.org/10.1038/nrc2355
  25. Strombeck DR, Gribble D. Chronic active hepatitis in the dog. J Am Vet Med Assoc 1978; 173: 380-386.
  26. Strombeck DR, Miller LM, Harrold D. Effects of corticosteroid treatment on survival time in dogs with chronic hepatitis: 151 cases (1977-1985). J Am Vet Med Assoc 1988; 193: 1109-1113.
  27. Takahashi R, Yoshitomi M, Yutani S, Shirahama T, Noguchi M, Yamada A, et al. Current status of immunotherapy for the treatment of biliary tract cancer. Hum Vaccin Immunother 2013; 9: 1069-1072. https://doi.org/10.4161/hv.23844
  28. Trigo FJ, Thompson H, Breeze RG, Nash AS. The pathology of liver tumours in the dog. J Comp Pathol 1982; 92: 21-39. https://doi.org/10.1016/0021-9975(82)90040-8
  29. van den Ingh TS, Van Winkle T, Cullen JM, Charles JA, Desmet VJ. Morphological classification of parenchymal disorders of the canine and feline liver: 2. Hepatocellular death, hepatitis and cirrhosis. In: WSAVA Liver Standardization Group, Rothuizen J, Bunch S, Charles J, Cullen J, Desmet V, editors. WSAVA Standards for clinical and histological diagnosis of canine and feline liver diseases. Amsterdam: Elsevier. 2006:85-101.
  30. Weng HL, Cai WM, Liu RH. Animal experiment and clinical study of effect of gamma-interferon on hepatic fibrosis. World J Gastroenterol 2001; 7: 42-48. https://doi.org/10.3748/wjg.v7.i1.42