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Autoreactive factors identify tumor-host heterogeneity and responsiveness to immunotherapy

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Summary

The heterogeneity of tumor-bearing animals was defined by the presence of an autoreactive antibody and cell agglutination factor in the sera of leukemic mice. The presence of this antibody, which could only be detected by its ability to lyse neuraminidase-treated spleen cells, correlated directly with the survival of the animals treated with active, specific immunotherapy. The results indicate that heterogeneity in hosts can be identified, and that autoreactive factors may be predictive for the individual response to immunotherapy and play a role in the establishment of the tumor-host relationship.

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References

  1. Bekesi JG, Holland JF (1972) Combined chemotherapy and immunotherapy of transplantable and spontaneous murine leukemia in DBA/2 and aKR mice. Recent Results Cancer Res 47:357–369

    Google Scholar 

  2. Cantrell JL, Killion JJ, Kollmorgen GM (1976) Correlations between humoral immunity and successful chemotherapy-immunotherapy. Cancer Res 36:3051–3057

    Google Scholar 

  3. Cowan WK (1962) Blood group antigens of human gastrointestinal carcinoma cells. Br J Cancer 16:535–539

    Google Scholar 

  4. Devlin RG, McCurdy JD, Baronowsky PE (1974a) Mixed lymphocyte reactivity against normal cells by splenic lymphocytes from tumor-bearing mice. I. Studies of vigorous immunoresponsiveness induced in F1 mice by parental strain tumor cells. J Exp Med 139:224–229

    Google Scholar 

  5. Devlin RG, McCurdy JD, Baronowsky PE (1974b) Mixed lymphocyte reactivity against normal cells by splenic lymphocytes from tumor-bearing mice. II. Studies of autoimmune-like activity in complete syngeneic and semisyngeneic systems. J Exp Med 139:230–237

    Google Scholar 

  6. Devlin RG, Baugh LE, McCurdy JD (1975) Studies on antilymphocytic autoimmune reactions in L1210-bearing mice. Cell Immunol 17:156–164

    Google Scholar 

  7. Fidler IJ (1973) Selection of successive tumor lines for metastasis. Nature 242:148–149

    Google Scholar 

  8. Fidler IJ (1978) Tumor heterogeneity and the biology of cancer invasion and metastasis. Cancer Res 38:2651–2660

    Google Scholar 

  9. Fidler IJ, Kripke ML (1980) Tumor cell antigenicity, host immunity, and cancer metastasis. Cancer Immunol Immunother 7:201–205

    Google Scholar 

  10. Gale DG, MacLennan ICM (1977) Cytotoxic antibody in acute myeloblastic leukemia during immunotherapy: Lack of tumor specificity. Br J Cancer 35:280–287

    Google Scholar 

  11. Gatenby PA, Basten A, Tattersall MHN et al. (1980) Autoantibodies in cancer patients given Corynebacterium parvum levamisole immunotherapy. Lancet 1:1082–1083

    Google Scholar 

  12. Gotze D, Ferrone S (1972) A rapid micromethod for direct H-2 typing of mouse cultured lymphoid cells. J Immunol Methods 1:203–206

    Google Scholar 

  13. Gray BN (1976) Naturally occurring human antibody to neuraminidase-treated human lymphocytes. J Natl Cancer Inst 56:211–214

    Google Scholar 

  14. Gutterman JU (1977) Cancer systemic active immunotherapy today — Prospects for tommorow. Cancer Immunol Immunother 2:1–9

    Google Scholar 

  15. Guy K, DiMario U, Irvine WJ et al. (1981) Circulating immune complexes and autoantibodies in lung cancer. Br J Cancer 43:276–283

    Google Scholar 

  16. Hakomori SI, Koscielak J, Bloch KJ, Jeanloz RW (1967) Immunologic relationship between blood group substances and a fucose-containing glycolipid of human adenocarcinoma. J Immunol 98:31–38

    Google Scholar 

  17. Hedley DW, McElwain TJ, Currie GA (1978) Specific active immunotherapy does not prolong in surgically treated patients with stage IIB malignant melanoma and may promote early recurrence. Br J Cancer 37:491–496

    Google Scholar 

  18. Heidrick ML, Ryan WL, Curtis GL (1978) Stimulation of malignant skin cells by antibody to normal skin cells of mice. J Natl Cancer Inst 60:1419–1425

    Google Scholar 

  19. Hersh EM, Gutterman JU, Mavligit G (1973) Immunotherapy of cancer in man. Thomas, Springfield

    Google Scholar 

  20. Hughes RC, Sanford B, Jeanloz RW (1972) Regeneration of the surface glycoproteins of a transplantable mouse tumor cell after treatment with neuraminidase. Proc Natl Acad Sci USA 69:942–945

    Google Scholar 

  21. Johannsen R, Sedlacek HH, Schmidtberger R (1979) Characteristics of cytotoxic antibodies against neuraminidase-treated lymphocytes in man. J Natl Cancer Inst 62:733–742

    Google Scholar 

  22. Kassulke JT, Stutman O, Yunis EJ (1971) Blood-group isoantigens in leukemic cells: Reversibility of isoantigenic changes by neuraminidase. J Natl Cancer Inst 46:1201–1208

    Google Scholar 

  23. Killion JJ (1977) The immunotherapeutic value of a L1210 tumor cell vaccine depends upon the expression of cell-surface carbohydrates. Cancer Immunol Immunother 3:87–91

    Google Scholar 

  24. Killion JJ (1978a) Immunotherapy with tumor cell subpopulations. I. Active specific immunotherapy of L1210 leukemia. Cancer Immunol Immunother 4:115–119

    Google Scholar 

  25. Killion JJ (1978b) Immunotherapy with tumor cell subpopulations. II. Therapy of drug-resistant L1210 leukemia and EL4 lymphoma. Cancer Immunol Immunother 15:21–26

    Google Scholar 

  26. Killion JJ (1978c) Immunotherapy with tumor cell subpopulations. III. Interaction between specific and nonspecific immunostimulants. Cancer Immunol Immunother 5:27–30

    Google Scholar 

  27. Killion JJ, Kollmorgen GM (1976) Isolation of immunogenic tumor cells by cell affinity chromatography. Nature 259:674–676

    CAS  PubMed  Google Scholar 

  28. LeFever AV, Killion JJ, Kollmorgen GM (1976) Active immunotherapy of L1210 leukemia with neuraminidase-treated, drug-resistant L1210 sublines. Cancer Immunol Immunother 1:211–217

    Google Scholar 

  29. McCredie KB, Bodey GP, Freireich E et al. (1981) Chemoimmunotherapy of adult acute leukemia. Cancer 47:1256–1261

    Google Scholar 

  30. McCune CS, Patterson WB, Henshaw EC (1979) Active specific immunotherapy with tumor cells and Corynebacterium parvum, a phase I study. Cancer 43:1619–1623

    Google Scholar 

  31. McCune CS, Schapira DV, Henshaw EC (1981) Specific immunotherapy of advanced renal carcinoma: Evidence for the polyclonality of metastases. Cancer 47:1984–1987

    Google Scholar 

  32. Nelson DS (1977) Autoantibodies in cancer patients. Pathology 9:155–160

    Google Scholar 

  33. Pierotti MA, Colnaghi MI (1975) Natural antibodies directed against murine lymphosarcoma cells. J Natl Cancer Inst 55:945–949

    Google Scholar 

  34. Risser R, Grunwald DJ (1981) Production of anti-self H-2 antibodies by hybrid mice immune to a viral tumor. Nature 289:563–568

    Google Scholar 

  35. Rogentine GN (1975) Naturally occurring human antibody to neuraminidase-treated lymphocytes. Antibody levels in normal subjects, cancer patients, and subjects with immunodeficiency. J Natl Cancer Inst 54:1307–1311

    Google Scholar 

  36. Rogentine GN, Plocinik BA (1974) Carbohydrate inhibition studies of the naturally occurring human antibody to neuraminidase-treated human lymphocytes. J Immunol 113:848–858

    Google Scholar 

  37. Rosenberg SA, Rogentine GN (1972) Natural human anti-bodies to “hidden” membrane components. Nature 239:203–204

    Google Scholar 

  38. Rosenberg SA, Schwarz S (1974) Murine autoantibodies to a cryptic membrane antigen: Possible explanation for neuraminidase-induced increase in cell immunogenicity. J Natl Cancer Inst 52:1151–1155

    Google Scholar 

  39. Ryan WL, Curtis GL, Heidrick ML et al. (1980) Autoantibody and tumor promotion. Proc. Soc Exp Biol Med 163:212–215

    Google Scholar 

  40. Sanford BH, Codington JF (1971) Further studies on the effect of neuraminidase on tumor cell transplantability. Tissue Antigens 1:153–161

    Google Scholar 

  41. Sethi KK, Brandis H (1972) In vitro cytotoxicity of normal serum factor(s) on neuraminidase-treated Ehrlich ascites tumor cells and murine leukemia L1210 cells. Z Immunol-Forsch 143:426–429

    Google Scholar 

  42. Sethi KK, Brandis H (1973) Synergistic cytotoxic effect of macrophages and normal mouse serum on neuraminidase-treated murine leukemia cells. Eur J Cancer 9:809–817

    Google Scholar 

  43. Simmons RL, Rios AJ (1971) Immunotherapy of cancer: Immunospecific rejection of tumors in recipients of neuraminidase-treated cells plus BCG. Science 174:591–595

    Google Scholar 

  44. Springer GF, Desai R, Scanlon EF (1976) Blood group MN precursors as human breast carcinoma-associated antigens and “naturally” occurring human cytotoxins against them. Cancer 37:169–176

    Google Scholar 

  45. Wallenbrock MA, Killion JJ (1978) Isolation of high-rate DNA synthetic cells kby Con A chromatography. J Cell Physiol 95:151–158

    Google Scholar 

  46. Whitehouse JMA, Holborow EJ (1971) Smooth muscle antibody in malignant disease. Br Med J 4:511–513

    Google Scholar 

  47. Whittaker JA, Bailey-Wood R, Hutchins S (1980) Active immunotherapy for the treatment of acute myelogenous leukemia: Report of two controlled trials. Br J Haematol 45:389–400

    Google Scholar 

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Killion, J.J., Baker, J.R. Autoreactive factors identify tumor-host heterogeneity and responsiveness to immunotherapy. Cancer Immunol Immunother 12, 111–117 (1982). https://doi.org/10.1007/BF00205368

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  • DOI: https://doi.org/10.1007/BF00205368

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