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Immunodeficient Mouse Models of Lymphoid Tumors

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Abstract

Severe combined immunodeficient (SCID) mice lack functional T- and B-cells and readily accept human xenografts, including hematopoietic malignancies.Accordingly, SCID mice have been used to study the growth and behavior of lymphoid tumors in vivo. The SCID mouse models of disease mimic human diseases and have provided valuable information. However, this mouse strain has some residual immunity that somewhat limits posttransplantation growth of human xenografts. Recently, the SCID mutation was backcrossed onto the nonobese diabetic (NOD) strain background. The result was an animal with additional immunological defects beyond those seen in SCID mice.The NOD/SCID strain appears to be more promising as a tool for xenotransplantation of lymphoid tumors. Moreover, these SCID and NOD/SCID mouse models have been used to develop novel therapeutic strategies. Results from such studies may also help to elucidate the pathogenesis of lymphoid tumors.

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References

  1. Bosma GC, Custer RP, Bosma MJ. A severe combined immunodeficiency mutation in the mouse.Nature. 1983;301:527–530.

    Article  CAS  PubMed  Google Scholar 

  2. Flavell DJ. Modelling human leukemia and lymphoma in severe combined immunodeficient (SCID) mice: practical applications.Hematol Oncol. 1996;14:67–82.

    Article  CAS  PubMed  Google Scholar 

  3. Bankert RB, Hess SD, Egilmez NK. SCID mouse models to study human cancer pathogenesis and approaches to therapy: potential, limitations, and future directions.Front Biosci. 2002;7:c44–62.

    PubMed  Google Scholar 

  4. Greiner DL, Shultz LD, Yates J, et al. Improved engraftment of human spleen cells in NOD/LtSz-scid/scid mice as compared with C.B-17-scid/scid mice.Am J Pathol. 1995;146:888–902.

    PubMed  PubMed Central  CAS  Google Scholar 

  5. Shultz LD, Schweitzer PA, Christianson SW, et al. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice.J Immunol. 1995;154:180–191.

    CAS  PubMed  Google Scholar 

  6. Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H. Adult T-cell leukemia: clinical and hematologic features of 16 cases.Blood. 1977;50:481–492.

    PubMed  CAS  Google Scholar 

  7. Uchiyama T. Human T cell leukemia virus type I (HTLV-I) and human diseases.Annu Rev Immunol. 1997;15:15–37.

    Article  CAS  PubMed  Google Scholar 

  8. Yoshida M. Multiple viral strategies of HTLV-1 for dysregulation of cell growth control.Annu Rev Immunol. 2001;19:475–496.

    Article  CAS  PubMed  Google Scholar 

  9. Kondo A, Imada K, Hattori T, et al. A model of in vivo cell proliferation of adult T-cell leukemia.Blood. 1993;82:2501–2509.

    PubMed  CAS  Google Scholar 

  10. Feuer G, Zack JA, Harrington WJ Jr, et al. Establishment of human T-cell leukemia virus type I T-cell lymphomas in severe combined immunodeficient mice.Blood. 1993;82:722–731.

    PubMed  CAS  Google Scholar 

  11. Imada K, Takaori-Kondo A, Akagi T, et al. Tumorigenicity of human T-cell leukemia virus type I-infected cell lines in severe combined immunodeficient mice and characterization of the cells proliferating in vivo.Blood. 1995;86:2350–2357.

    PubMed  CAS  Google Scholar 

  12. Imada K, Takaori-Kondo A, Sawada H, et al. Serial transplantation of adult T cell leukemia cells into severe combined immunodeficient mice.Jpn J Cancer Res. 1996;87:887–892.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Takaori-Kondo A, Imada K, Yamamoto I, et al. Parathyroid hormone- related protein-induced hypercalcemia in SCID mice engrafted with adult T-cell leukemia cells.Blood. 1998;91:4747–4751.

    PubMed  CAS  Google Scholar 

  14. Bunn PA Jr, Schechter GP, Jaffe E, et al. Clinical course of retrovirus- associated adult T-cell lymphoma in the United States.N Engl J Med. 1983;309:257–264.

    Article  PubMed  Google Scholar 

  15. Johannessen I, Crawford DH. In vivo models for Epstein-Barr virus (EBV)-associated B cell lymphoproliferative disease (BLPD).Rev Med Virol. 1999;9:263–277.

    Article  CAS  PubMed  Google Scholar 

  16. Mosier DE, Gulizia RJ, Baird SM, Wilson DB. Transfer of a functional human immune system to mice with severe combined immunodeficiency.Nature. 1988;335:256–259.

    Article  CAS  PubMed  Google Scholar 

  17. Rowe M, Young LS, Crocker J, Stokes H, Henderson S, Rickinson AB. Epstein-Barr virus (EBV)-associated lymphoproliferative disease in the SCID mouse model: implications for the pathogenesis of EBV-positive lymphomas in man.J Exp Med. 1991;173:147–158.

    Article  CAS  PubMed  Google Scholar 

  18. Mosier DE. Viral pathogenesis in hu-PBL-SCID mice.Semin Immunol. 1996;8:255–262.

    Article  CAS  PubMed  Google Scholar 

  19. Picchio GR, Kobayashi R, Kirven M, Baird SM, Kipps TJ, Mosier DE. Heterogeneity among Epstein-Barr virus-seropositive donors in the generation of immunoblastic B-cell lymphomas in SCID mice receiving human peripheral blood leukocyte grafts.Cancer Res. 1992;52:2468–2477.

    PubMed  CAS  Google Scholar 

  20. Amadori A, Veronese ML, Mazza MR, et al. Lymphoma induction by human B cells in scid mice.Leukemia. 1992;6(suppl 3):23S-25S.

    PubMed  Google Scholar 

  21. Veronese ML, Vneronesi A, D’Andrea E, et al. Lymphoproliferative disease in human peripheral blood mononuclear cell-injected SCID mice, I: T lymphocyte requirement for B cell tumor generation.J Exp Med. 1992;176:1763–1767.

    Article  CAS  PubMed  Google Scholar 

  22. Johannessen I, Asghar M, Crawford DH. Essential role for T cells in human B-cell lymphoproliferative disease development in severe combined immunodeficient mice.Br J Haematol. 2000;109:600–610.

    Article  CAS  PubMed  Google Scholar 

  23. Johannessen I, Perera SM, Gallagher A, Hopwood PA, Thomas JA, Crawford DH. Expansion in scid mice of Epstein-Barr virus— associated post-transplantation lymphoproliferative disease biopsy material.J Gen Virol. 2002;83:173–178.

    Article  CAS  PubMed  Google Scholar 

  24. Ghetie MA, Richardson J, Tucker T, Jones D, Uhr JW, Vitetta ES. Disseminated or localized growth of a human B-cell tumor (Daudi) in SCID mice.Int J Cancer. 1990;45:481–485.

    Article  CAS  PubMed  Google Scholar 

  25. Waller EK, Kamel OW, Cleary ML, et al. Growth of primary T-cell non-Hodgkin’s lymphomata in SCID-hu mice: requirement for a human lymphoid microenvironment.Blood. 1991;78:2650–2665.

    PubMed  CAS  Google Scholar 

  26. Itoh T, Shiota M, Takanashi M, et al. Engraftment of human non- Hodgkin lymphomas in mice with severe combined immunodeficiency.Cancer. 1993;72:2686–2694.

    Article  CAS  PubMed  Google Scholar 

  27. Kapp U, Wolf J, von Kalle C, et al. Preliminary report: growth of Hodgkin’s lymphoma derived cells in immune compromised mice.Ann Oncol. 1992;3(suppl 4):21–23.

    Article  PubMed  Google Scholar 

  28. Bargou RC, Mapara MY, Zugck C, et al. Characterization of a novel Hodgkin cell line, HD-MyZ, with myelomonocytic features mimicking Hodgkin’s disease in severe combined immunodeficient mice.J Exp Med. 1993;177:1257–1268.

    Article  CAS  PubMed  Google Scholar 

  29. Wolf J, Kapp U, Bohlen H, et al. Peripheral blood mononuclear cells of a patient with advanced Hodgkin’s lymphoma give rise to permanently growing Hodgkin-Reed Sternberg cells.Blood. 1996;87:3418–3428.

    PubMed  CAS  Google Scholar 

  30. Kapp U, Wolf J, Hummel M, et al. Hodgkin’s lymphoma-derived tissue serially transplanted into severe combined immunodeficient mice.Blood. 1993;82:1247–1256.

    PubMed  CAS  Google Scholar 

  31. Hudson WA, Li Q, Le C, Kersey JH. Xenotransplantation of human lymphoid malignancies is optimized in mice with multiple immunologic defects.Leukemia. 1998;12:2029–2033.

    Article  CAS  PubMed  Google Scholar 

  32. Fusetti L, Pruneri G, Gobbi A, et al. Human myeloid and lymphoid malignancies in the non-obese diabetic/severe combined immunodeficiency mouse model: frequency of apoptotic cells in solid tumors and efficiency and speed of engraftment correlate with vascular endothelial growth factor production.Cancer Res. 2000;60:2527–2534.

    PubMed  CAS  Google Scholar 

  33. Phillips KE, Herring B, Wilson LA, et al. IL-2Ralpha-Directed monoclonal antibodies provide effective therapy in a murine model of adult T-cell leukemia by a mechanism other than blockade of IL-2/IL-2Ralpha interaction.Cancer Res. 2000;60:6977–6984.

    PubMed  CAS  Google Scholar 

  34. Liu Y, Dole K, Stanley JR, et al. Engraftment and tumorigenesis of HTLV-1 transformed T cell lines in SCID/bg and NOD/SCID mice.Leuk Res. 2002;26:561–567.

    Article  PubMed  Google Scholar 

  35. Tan C, Waldmann TA. Proteasome inhibitor PS-341, a potential therapeutic agent for adult T-cell leukemia.Cancer Res. 2002;62:1083–1086.

    PubMed  CAS  Google Scholar 

  36. Bellamy WT, Richter L, Frutiger Y, Grogan TM. Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies.Cancer Res. 1999;59:728–733.

    PubMed  CAS  Google Scholar 

  37. Salven P, Teerenhovi L, Joensuu H. A high pretreatment serum vascular endothelial growth factor concentration is associated with poor outcome in non-Hodgkin’s lymphoma.Blood. 1997;90:3167–3172.

    PubMed  CAS  Google Scholar 

  38. Salven P, Teerenhovi L, Joensuu H. A high pretreatment serum basic fibroblast growth factor concentration is an independent predictor of poor prognosis in non-Hodgkin’s lymphoma.Blood. 1999;94:3334–3339.

    PubMed  CAS  Google Scholar 

  39. Bertolini F, Fusetti L, Mancuso P, et al. Endostatin, an antiangiogenic drug, induces tumor stabilization after chemotherapy or anti- CD20 therapy in a NOD/SCID mouse model of human high-grade non-Hodgkin lymphoma.Blood. 2000;96:282–287.

    PubMed  CAS  Google Scholar 

  40. Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma.N Engl J Med. 1999;341:1565–1571.

    Article  CAS  PubMed  Google Scholar 

  41. Lentzsch S, Rogers MS, LeBlanc R, et al. S-3-Amino-phthalimidoglutarimide inhibits angiogenesis and growth of B-cell neoplasias in mice.Cancer Res. 2002;62:2300–2305.

    PubMed  CAS  Google Scholar 

  42. Gruss HJ, Boiani N, Williams DE, Armitage RJ, Smith CA, Goodwin RG. Pleiotropic effects of the CD30 ligand on CD30- expressing cells and lymphoma cell lines.Blood. 1994;83:2045–2056.

    PubMed  CAS  Google Scholar 

  43. Tian ZG, Longo DL, Funakoshi S, et al. In vivo antitumor effects of unconjugated CD30 monoclonal antibodies on human anaplastic large-cell lymphoma xenografts.Cancer Res. 1995;55:5335–5341.

    PubMed  CAS  Google Scholar 

  44. Wahl AF, Klussman K, Thompson JD, et al. The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin’s disease.Cancer Res. 2002;62:3736–3742.

    PubMed  CAS  Google Scholar 

  45. Nagy ZA, Hubner B, Lohning C, et al. Fully human, HLA-DRspecific monoclonal antibodies efficiently induce programmed death of malignant lymphoid cells.Nat Med. 2002;8:801–807.

    Article  CAS  PubMed  Google Scholar 

  46. Barth S, Huhn M, Matthey B, et al. Recombinant anti-CD25 immunotoxin RFT5(SCFV)-ETA° demonstrates successful elimination of disseminated human Hodgkin lymphoma in SCID mice.Int J Cancer. 2000;86:718–724.

    Article  CAS  PubMed  Google Scholar 

  47. Barth S, Huhn M, Matthey B, et al. Ki-4(scFv)-ETA°, a new recombinant anti-CD30 immunotoxin with highly specific cytotoxic activity against disseminated Hodgkin tumors in SCID mice.Blood. 2000;95:3909–3914.

    PubMed  CAS  Google Scholar 

  48. Boyle TJ, Berend KR, DiMaio JM, Coles RE, Via DF, Lyerly HK. Adoptive transfer of cytotoxic T lymphocytes for the treatment of transplant-associated lymphoma.Surgery. 1993;114:218–225.

    PubMed  CAS  Google Scholar 

  49. Lacerda JF, Ladanyi M, Louie DC, Fernandez JM, Papadopoulos EB, O’Reilly RJ. Human Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes home preferentially to and induce selective regressions of autologous EBV-induced B cell lymphoproliferations in xenografted C.B-17 scid/scid mice.J Exp Med. 1996;183:1215–1228.

    Article  CAS  PubMed  Google Scholar 

  50. Cotter FE, Waters J, Cunningham D. Human Bcl-2 antisense therapy for lymphomas.Biochim Biophys Acta. 1999;1489:97–106.

    Article  CAS  PubMed  Google Scholar 

  51. Cotter FE, Johnson P, Hall P, et al. Antisense oligonucleotides suppress B-cell lymphoma growth in a SCID-hu mouse model.Oncogene. 1994;9:3049–3055.

    PubMed  CAS  Google Scholar 

  52. Mohammad R, Abubakr Y, Dan M, et al. Bcl-2 antisense oligonucleotides are effective against systemic but not central nervous system disease in severe combined immunodeficient mice bearing human t(14;18) follicular lymphoma.Clin Cancer Res. 2002;8:1277–1283.

    PubMed  CAS  Google Scholar 

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Correspondence to Kazunori Imada.

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Imada, K. Immunodeficient Mouse Models of Lymphoid Tumors. Int J Hematol 77, 336–341 (2003). https://doi.org/10.1007/BF02982640

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  • DOI: https://doi.org/10.1007/BF02982640

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