Adoptive Immunotherapy of Leukemia by Endotoxin-Induced Modulation of the Graft-versus-Host Reaction

  • Robert L. Truitt


Allogeneic bone marrow transplantation is used for the treatment of a variety of hematological dyscrasias including aplastic anemia, severe combined immunodeficiency disease, and leukemia (Thomas et al., 1975; Bortin and Rimm, 1977; Storb et al., 1978; Bortin and Rimm, 1978, 1981). Two of the major problems associated with allogeneic marrow transplantation are the immunologic attack of grafted cells or their progeny against histocompatibility antigens on host cells, i.e., graft-versus-host (GVH) reactivity, and susceptibility of the immuno-suppressed host to endogenous and exogenous sources of infection (Thomas et al., 1975). Attempts to resolve these problems have consumed a great deal of experimental and clinical effort with moderate, but by no means complete success.


Spleen Cell Allogeneic Bone Marrow Transplantation Adoptive Immunotherapy Hemopoietic Stem Cell Donor Mouse 
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  1. Boggs, S. S., Wilson, S. M., and Smith, W. W., 1973, Effects of endotoxin on hematopoi-esis in irradiated and nonirradiated W JWv mice, Radiât. Res. 56:481.PubMedCrossRefGoogle Scholar
  2. Bortin, M. M., 1974, Graft-versus-leukemia, in: Cluneal Immunobiology, Vol. 2 (F. H. Bach and R. A. Good, eds.), pp. 287–306, Academic Press, New York.Google Scholar
  3. Bortin, M. M., and Rimm, A. A., 1977, Severe combined immunodeficiency disease: Characterization of the disease and results of transplantation, J. Am. Med. Assoc. 238: 591.CrossRefGoogle Scholar
  4. Bortin, M. M., and Rimm, A. A., 1978, Bone marrow transplantation for acute myeloblas-tic leukemia,J. Am. Med. Assoc. 240:1245.CrossRefGoogle Scholar
  5. Bortin, M. M., and Rimm, A. A., 1981, Allogeneic bone marrow transplantation for 144 patients with severe aplastic anemia,J. Am. Med. Assoc. 245:1132.CrossRefGoogle Scholar
  6. Bortin, M. M., and Truitt, R. L., 1977, AKR T cell acute lymphoblastic leukemia: A model for human T cell leukemia, Biomediane 26:315.Google Scholar
  7. Bortin, M. M., Rimm, A. A., and Saltzstein, E. C., 1973, Graft-versus-leukemia: Quantification of adoptive immunotherapy in murine leukemia, Science 179:811.PubMedCrossRefGoogle Scholar
  8. Bortin, M. M., Truitt, R. L., and Rimm, A. A., 1978, Nonspecific adoptive immunotherapy of T cell acute lymphoblastic leukemia in AKR mice: A model for the treatment of T cell leukemia in man, in: The Handbook of Cancer Immunology, Vol. 5, Immunotherapy (H. Waters, ed.), pp. 401–429, Garland STPM Press, New York.Google Scholar
  9. Chedid, L., 1973, Possible role of endotoxemia during immunologic imbalance,J. Infect. Dis. 128(Suppl.):112.PubMedCrossRefGoogle Scholar
  10. Connell, M. St. J., and Wilson, R., 1965, The treatment of x-irradiated germfree CFW and C3H mice with isologous and homologous bone marrow, Life Sci. 4:721.PubMedCrossRefGoogle Scholar
  11. Damais, C., Lamensans, A., and Chedid, L., 1972, Endotoxines bacteriennes et maladie homologue du nouveau-né, C. R. Acad. Sci. 274:1113.Google Scholar
  12. Elkins, W. L., 1971, Cellular immunology and the pathogenesis of graft-versus-host reactions, Prog. Allergy 15:78.PubMedCrossRefGoogle Scholar
  13. Gale, R. P., and the UCLA Bone Marrow Transplant Unit, 1979, Current status of bone marrow transplantation in acute leukemia, Transplant. Proc. 11:1920.PubMedGoogle Scholar
  14. Galley, C. B., Walker, R. I., Ledney, G. D., and Gambrill, M. R., 1975, Evaluation of biologic activity of ferric chloride-treated endotoxin in mice, Exp. Hematol. 3:197.PubMedGoogle Scholar
  15. Glucksberg, H., Storb, R., Fefer, A., Buckner, C. D., Neiman, P. E., Clift, R. A., Lerner, K. G., and Thomas, E. D., 1974, Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors, Transplantation 18: 295.PubMedCrossRefGoogle Scholar
  16. Grebe, S. C., and Streilein, J. W., 1976, Graft-versus-host reactions: A review, Adv. Immunol. 22:119.PubMedCrossRefGoogle Scholar
  17. Grohsman, J., and Nowotny, A., 1972, the immune recognition of TA3 tumors, its facilitation by endotoxin, and abrogation by ascites fluid,J. Immunol. 109:1090.Google Scholar
  18. Heit, H., Heit, W., Kohne, E., Fleidner, T. M., and Hughes, P., 1977, Allogeneic bone marrow transplantation in conventional mice. I. Effect of antibiotic therapy on long term survival of allogeneic chimeras, Blut 35:143.PubMedCrossRefGoogle Scholar
  19. Jones, J. M., Wilson, R., and Bealmear, P. M., 1971, Mortality and gross pathology of secondary disease in germfree mouse radiation chimeras, Radiat. Res. 45:577.PubMedCrossRefGoogle Scholar
  20. Jutila, J. W., 1973, Etiology of the wasting diseases,J. Infect. Dis. 128(Suppl.):99.CrossRefGoogle Scholar
  21. Keast, D., 1973, Role of bacterial endotoxin in the graft-vs-host syndrome, J. Infect. Dis. 128(Suppl.):104.PubMedCrossRefGoogle Scholar
  22. Korngold, R., and Sprent, J., 1978, Lethal graft-versus-host disease after bone marrow transplantation across major histocompatibility barriers in mice, J. Exp. Med. 148: 1687.PubMedCrossRefGoogle Scholar
  23. LeFeber, W. P., Truitt, R. L., Rose, W. C., and Bortin, M. M., 1977, Graft-versus-leuke-mia: Donor selection for adoptive immunotherapy in mice, in: Experimental Hematology Today1977 (S. J. Baum and G. D. Ledney, eds.), pp. 239–246, Springer-Verlag, Berlin.Google Scholar
  24. Liacopoulos, P., and Merchant, B., 1969, Effet du traitement des donneurs avec des endotoxines sur la maladie homologue des receveurs adultes irradiés, in: La structure et les effets biologiques des produits bactériens provenants de germes Gram-négatifs (L. Chedid, ed.), pp. 341–356, Colloq. Int. sur les Endotoxines, CNRS No. 174, Paris.Google Scholar
  25. Liacopoulos, P., Merchant, B., and Harrel, R. E., 1967, Inhibition de la maladie homologue par un traitement des couris donneuses avec des antigenes bacteriens, Pathol. Biol. 15:587.PubMedGoogle Scholar
  26. MacDonald, H. R., Cerottini, J.-C., Ryser, J.-E., Maryanski, J. L., Taswell, C., Widmer, M. B., and Brunner, K. T., 1980, Quantitation and cloning of cytolytic T lymphocytes and their precursors, Immunol. Rev. 51:93.PubMedCrossRefGoogle Scholar
  27. Mclntire, R., and Gale, R. P., 1981, Relationship between graft-versus-leukemia and graft-versus-host in man — UCLA experience, in: Graft-versus-Leukemia in Man and Animal Models (J. P. OKunewick and R. F. Meredith, eds.), pp. 1–9, CRC Press, Boca Raton, Fla.Google Scholar
  28. Miller, R. G., Teh, H.-S., Harley, E., and Phillips, R. A., 1977, Quantitative studies of the activation of cytotoxic lymphocyte precursor cells, Immunol. Rev. 35:38.PubMedCrossRefGoogle Scholar
  29. Morrison, D. C., and Ryan, J. L., 1979, Bacterial endotoxins and host immune responses, Adv. Immunol. 28:293.PubMedCrossRefGoogle Scholar
  30. Okunewick, J. P., and Meredith, R. F. (eds.), 1981, Graf t-versus-Leukemia in Man and Animal Models, CRC Press, Boca Raton, Fla.Google Scholar
  31. Okunewick, J. P., Meredith, R. F., Brozovich, B. J., Seeman, P. R., and Magliere, K., 1980, Exponential relationship between spleen cell concentration and fatal graft-versus-host response after transplantation of allogeneic spleen-marrow cell mixtures, Transplantation 29:507.PubMedCrossRefGoogle Scholar
  32. Parr, I., Wheeler, E., and Alexander, P., 1973, Similarities of the anti-tumor actions of endotoxin, lipid A and double-stranded RNA, Br. J. Cancer 27:370.PubMedCrossRefGoogle Scholar
  33. Powles, R. L., Morgenstern, G., Clink, H. M., Hedley, D., Bandini, G., Lumley, H., Watson, J. G., Lawson, D., Spence, D., Barrett, A., Jameson, B., Lawler, S., Kay, H. E. M., and McElwain, T.I., 1980, The place of bone-marrow transplantation in acute myelogenous leukaemia, Lancet 1:1047.PubMedCrossRefGoogle Scholar
  34. Rampy, P. A., and Jutila, J. W., 1979, Influence of lipopolysaccharide on graft-versus-host reactivity of lipopolysaccharide-unresponsive C3H JHeJ mice, Infect. Immun. 26: 137.PubMedGoogle Scholar
  35. Reed, L. J., and Muench, H. A., 1938, A simple method of estimating fifty percent end-points, Am. J. Hyg. 27:493.Google Scholar
  36. Reed, N. D., and Jutila, J. W., 1965, Wasting disease induced with Cortisol acetate: Studies in germ-free mice, Science 150:356.PubMedCrossRefGoogle Scholar
  37. Rose, W. C., Rodey, G. E., Rimm, A. A., Truitt, R. L., and Bortin, M. M., 1976, Mitigation of graft-versus-host disease in mice by treatment of donors with bacterial endotoxin, Exp. Hematol. 4:90.PubMedGoogle Scholar
  38. Russell, P. S., 1960, Ehe weight-gain assay for runt disease in mice, Ann. X.Y. Acad. Sci. 87:445.CrossRefGoogle Scholar
  39. Siminovitch, L., McGulloch, E. A., and Till, J. E., 1963, The distribution of colony forming cells among spleen colonies,J. Cell. Comp. Physiol. 62:327.CrossRefGoogle Scholar
  40. Simonsen, M., 1962, Graft-versus-host reactions: Their natural history and applicability as tools of research, Prog. Allergy 6:349.PubMedGoogle Scholar
  41. Storb, R., Thomas, E. D., Weiden, P. L., Buckner, C. D., Clift, R. A., Tyler, A., Goodell, B. W., Johnson, E. L., Neiman, P. E., Sanders, J. E., and Singer, J., 1978, One-hundred-ten patients with aplastic anemia (AA) treated by marrow transplantation in Seattle, Transplant. Proc. 10:135.PubMedGoogle Scholar
  42. Thomas, E. D., Storb, R., Clift, R. A., Eefer, A., Johnson, F. L., Neiman, P. E., Lerner, K. G., Glucksberg, H., and Buckner, C. D., 1975, Bone marrow transplantation, N. Engl. J. Med. 292:832, 895.PubMedCrossRefGoogle Scholar
  43. Thomas, E. D., Buckner, C. D., Banaji, M., Clift, R. A., Fefer, A., Flournoy, N., Goodell, B. W., Hickman, R. O., Lerner, K. G., Neiman, P. E., Sale, G. E., Sanders, J. E., Singer, J., Stevens, M., Storb, R., and Weiden, P. L., 1977, One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation, Blood 49:511.PubMedGoogle Scholar
  44. Thomson, P. D., and Jutila, J. W., 1974, The suppression of graft-versus-host disease in mice by endotoxin-treated adherent spleen cells,J. Reticuloendothelial Soc. 16:327.Google Scholar
  45. Thomson, P. D., Rampy, P. A., and Jutila, J. W., 1978, A mechanism for the suppression of graft-vs-host disease with endotoxin,J. Immunol. 120:1340.PubMedGoogle Scholar
  46. Till, J. E., and McCulloch, E. A., 1961, A direct measurement of the radiation sensitivity of normal mouse bone marrow cells, Radiat. Res. 14:213.PubMedCrossRefGoogle Scholar
  47. Truitt, R. L., 1978a, Use of decontamination and a protected environment to prevent secondary disease following adoptive immunotherapy of acute leukemia in mice, in: Experimental Hematology Today1978 (S. J. Baum and G. D. Ledney, eds.), pp. 195–201, Springer-Verlag, Berlin.Google Scholar
  48. Truitt, R. L., 1978b, Application of germfree techniques to the treatment of leukemia in AKR mice by allogeneic bone marrow transplantation, in: The Handbook of Cancer Immunology, Vol. 5, Immunotherapy (H. Waters, ed.), pp. 431–452, Garland STPM Press, New York.Google Scholar
  49. Truitt, R. L., 1979, Successful adoptive immunotherapy of AKR spontaneous T cell leukemia following antibiotic decontamination and protective isolation, in: Clinical and Experimental Cnotobiotics (T. Elicdner, H. Heit, D. Niethammer, and H. Pfleger, eds.), pp. 215–220, Gustav Fischer Verlag, Stuttgart.Google Scholar
  50. Truitt, R. L., Rose, W. C., Rimm, A. A., and Bortin, M. M., 1978, Graft-versus-leukemia. VIII. Selective reduction in antihost reactivity without loss of antileukemic reactivity by treatment of donor mice with lipopolysaccharide, Exp. Hematol. 6:488.PubMedGoogle Scholar
  51. van Bekkum, D. W., and de Vries, M. J., (eds.), 1967, Radiation Chunaeras, Logos Press, London.Google Scholar
  52. van Bekkum, D. W., and Vos, O., 1961, Treatment of secondary disease in radiation chimaeras, Int. J. Radiât. Biol. 3:173.PubMedCrossRefGoogle Scholar
  53. van Bekkum, D. W., Roodenburg, J., Heidt, P. J., and van der Waaij, D., 1974, Mitigation of secondary disease of allogeneic mouse radiation chimaeras by modification of the intestinal microflora,J. Natl Cancer Inst. 52:401.PubMedGoogle Scholar
  54. Walker, R. L, 1978, The contribution of intestinal endotoxin to mortality in hosts with compromised resistance: A review, Exp. Hematol 6:172.PubMedGoogle Scholar
  55. Walker, R. I., Ledney, G. D., and Galley, C. B., 1975, Aseptic endotoxemia in radiation injury and graft-vs-host disease, Radiat. Res. 62:242.PubMedCrossRefGoogle Scholar
  56. Weiden, P. L., Flournoy, N., Thomas, E. D., Prentice, R., Fefer, A., Buckner, C. D., and Storb, R., 1979, Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts, N. Engl. J. Med. 300:1068.PubMedCrossRefGoogle Scholar
  57. Weiden, P. L., Flournoy, N., Sanders, J. E., Sullivan, K. M., and Thomas, E. D., 1981, Antileukemic effect of graft-versus-host disease contributes to improved survival after allogeneic marrow transplantation, Transplant. Proc. 13:248.PubMedGoogle Scholar
  58. Yang, C., and Nowotny, A., 1974, Effect of endotoxin on tumor resistance in mice, Infect. Immun. 9:95.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Robert L. Truitt
    • 1
  1. 1.May and Sigmund Winter Research LaboratoryMount Sinai Medical CenterMilwaukeeUSA

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