Anti-tumor antibody produced by human tumor-infiltrating and peripheral blood B lymphocytes (original) (raw)

Abstract

Cell suspensions from 69 human tumor biopsies and malignant effusions depleted of infiltrating T cells were incubated for 10–14 days with mitomycin-C-treated cells of the transformed T cell line MOT as feeder cells. B lymphocytes proliferated and differentiated as indicated by immunoglobulin (Ig) seerction in the culture supernatants (B cell expansion). Ig was present in culture supernatants of tumor cell suspensions incubated without MOT feeder cells (non-expanded cells), but the addition of MOT feeder cells to these cultures invariably resulted in a significant increase in Ig concentration. While IgG, IgA. and IgM isotypes were all detected in supernatants of both expanded- and nonexpanded tumor cell suspensions, the increase in total Ig induced by MOT feeder cells was mainly due to an increase in IgG. Peripheral blood B lymphocytes (PBBL) from 15 cancer patients and 4 healthy individuals were also successfully expanded by the same method. In these it was shown that IgA was the predominant Ig isotype. Using a modified enzyme-linked immunosorbent assay, IgG of 25/36 expansions from tumor cell suspensions showed reactivity with autologous tumor targets, and that from 10/13 expansions reacted with allogeneic tumor targets of the same histological diagnosis. No reactivity was found against tumor targets of different histology. IgG of 4/10 expansions of PBBL from cancer patients showed reactivity with allogeneic tumor targets of the same histology, while no reactivity was demonstrated against tumor targets of different histology. IgG of expanded PBBL from healthy individuals showed no reactivity against tumor targets. This method allows detailed study of the specific humoral antitumor immune response of intratumoral and peripheral blood B lymphocytes in cancer.

Access this article

Log in via an institution

Subscribe and save

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Topalian SL, Rosenberg SA (1991) Adoptive cellular therapy: basic principles. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds) Biologic therapy of cancer. Lippincott, Philadelphia, p 187
    Google Scholar
  2. Hurlimann J, Saraga P (1985) Mononuclear cells infiltrating human mammary carcinomas: immunohistochemical analysis with monoclonal antibodies. Int J Cancer 35: 753
    PubMed Google Scholar
  3. Whiteside TL, Miescher S, Hurlimann J, Moretta L, Von Fliedner V (1986) Clonal analysis and in situ characterization of lymphocytes infiltrating human breast carcinomas. Cancer Immunol Immunother 23: 169
    PubMed Google Scholar
  4. Ferguson A, Moore M, Fox H (1985) Expression of MHC products and leucocyte differentiation antigens in gynaecological neoplasms: an immunohistological analysis of the tumour cells and infiltrating leucocytes. Br J Cancer 52: 551
    PubMed Google Scholar
  5. Wolf GT, Hudson JL, Peterson KA, Miller HL, McClatchey KD (1986) Lymphocyte subpopulations infiltrating squamous carcinomas of the head and neck: correlations with extent of tumor and prognosis. Otolaryngol Head Neck Surg 95: 142
    PubMed Google Scholar
  6. Schoorl R, Brutel de la Rivière A, Borne AEGKr von dem, Feltkamp-Vroom TM (1976) Identification of T and B lymphocytes in human breast cancer with immunohistochemical techniques. Am J Pathol 84: 529
    PubMed Google Scholar
  7. Husby G, Hoagland PM, Strickland RG, Williams RC (1976) Tissue T and B cell infiltration of primary and metastatic cancer. J Clin Invest 57: 1471
    PubMed Google Scholar
  8. Stevens A, Klöter I, Roggendorf W (1988) Inflammatory infiltrates and natural killer cell presence in human brain tumors. Cancer 61: 738
    PubMed Google Scholar
  9. Vose BM, Moore M (1979) Suppressor cell activity of lymphocytes infiltrating human lung and breast tumours. Int J Cancer 24: 579
    PubMed Google Scholar
  10. Bröcker EB, Zwadlo G, Holzmann B, Macher E, Sorg C (1988) Inflammatory cell infiltrates in human melanoma at different stages of tumor progression. Int J Cancer 41: 562
    PubMed Google Scholar
  11. Withford P, Mallon EA, George WD, Campbell AM (1990) Flow cytometric analysis of tumor infiltrating lymphocytes in breast cancer. Br J Cancer 62: 971
    PubMed Google Scholar
  12. Sikora K, Alderson T, Philips J, Watson JV (1982) Human hybridomas from malignant gliomas. Lancet 1: 11
    PubMed Google Scholar
  13. Sikora K, Alderson T, Ellis J, Philips J, Watson J, (1983) Human hybridomas from patients with malignant diseases. Br J Cancer 47: 135
    PubMed Google Scholar
  14. Jerne NK, Henry C, Nordin AA, et al (1974) Plaque forming cells: methodology and theory. Transplant Rev 18: 130
    PubMed Google Scholar
  15. Henderson E, Miller G, Robinson J, Heston L (1977) Efficiency of transformation of lymphocytes by Epstein-Barr virus. Virology 76: 152
    PubMed Google Scholar
  16. Aman P, Ehlin-Henriksson B, Klein G (1984) Epstein-Barr virus susceptibility of normal human B lymphocyte populations. J Exp Med 159: 208
    PubMed Google Scholar
  17. Kozbor D, Croce CH (1985) Fusion partners for production of human monoclonal antibodies. In: Engleman EG, Foung SKH, Larrick J, Raubitschek A (eds) Human hybridomas and monoclonal antibodies, Plenum, New York, p 21
    Google Scholar
  18. Hirohata S, Jelinek DF, Lipsky PE (1988) T cell-dependent activation and differentiation of B cell proliferation by immobilized monoclonal antibodies to CD3. J Immunol 140: 3736
    PubMed Google Scholar
  19. Amoroso K Lipsky PE (1990) Frequency of human B cells that differentiate in response to anti-CD3-activated T cells. J Immunol 145: 3155
    PubMed Google Scholar
  20. Kelly PJ, Pascual V, Capra JD, Lipsky PE (1992) Anti-CD3-stimulated T cells induce the production of multiple Ig H chain isotypes by individual human peripheral B lymphocytes. J Immunol 148: 1294
    PubMed Google Scholar
  21. Barbuto JAM, Verastegui EL, Hersh EM (1993) The use of transformed T cell lines for clonal expansion of human B cells from peripheral blood, spleen, and tumor-infiltrating lymphocytes. Hybridoma 12: 115
    PubMed Google Scholar
  22. Hersh EM, Mavligit GM, Gutterman JU (1976) Immunodeficiency in cancer and the importance of immune evaluation of the cancer patient. Med Clin N Am 60: 623
    PubMed Google Scholar
  23. Miescher S, Whiteside TL, Carrel S, Von Fliedner V (1986) Functional properties of tumor-infiltrating and blood lymphocytes in patients with solid tumors: effects of tumor cells and their supernatants on proliferative responses of lymphocytes. J Immunol 136: 1899
    PubMed Google Scholar
  24. Lane HC, Fauci AS (1985) Immunologic abnormalities in the acquired immunodeficiency syndrome. Annu Rev Immunol 3: 477
    PubMed Google Scholar
  25. Saxon A, Feldhaus J, Robins RA (1976) Single step separation of human T and B cells using AET treated sheep red cells. J Immunol Methods 90: 221
    Google Scholar
  26. Thiele DL, Kurosaka M, Lipsky PE (1983) Phenotype of the accessory cell necessary for mitogen-stimulated T and B cell responses in human peripheral blood: delineation by its sensitivity to the lysomotropic agent,l-leucine methyl ester. J. Immunol 131: 2282
    PubMed Google Scholar
  27. Bishop GA, Hwang J (1992) Use of a cellular ELISA for the detection of cell surface antigens. Biotechniques 12: 326
    PubMed Google Scholar
  28. Henry C, Marbrook J, Vann DC, Kondlin D, Wofsy C (1980) Limiting dilution analysis. In: Mishell BB, Shiigi SM (eds) Selected methods in cellular immunology. Freeman, San Francisco, p 138
    Google Scholar
  29. Chandler HM, Cox JC, Healy K, MacGregor A, Premier RR, Hurrell JGR (1982) An investigation of the use of urease-antibody conjugates in enzyme immunoassays. J Immunol Methods 53: 187
    PubMed Google Scholar
  30. Douillard JY, Hoffman T, Herberman RB (1980) Enzyme-linked immunosorbent assay for screening monoclonal antibody production: use of intact cells as antigen. J Immunol Methods 39: 309
    PubMed Google Scholar
  31. Suter L, Bruggen J, Sorg C (1980) Use of an enzyme-linked immunosorbent assay (ELISA) for screening of hybridoma antibodies against cell surface antigens. J Immunol Methods 39: 407
    PubMed Google Scholar
  32. Hellström KE, Hellström I (1991) Principles of tumor immunity: tumor antigens. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds) Biologic therapy of cancer. Lippincott, Philadelphia, p 42
    Google Scholar
  33. Kawakami Y, Zakut R, Topalian SL, Stötter H, Rosenberg SA (1992) Shared human melanoma antigens. Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas. J Immunol 148: 638
    PubMed Google Scholar
  34. Sjögren HD, Hellström I, Bansal SC, Warner GA, Hellström KE (1972) Elution of “blocking factors” from human tumors, capable of abrogating tumor-cell destruction by specific immune lymphocytes. Int J Cancer 9: 274
    PubMed Google Scholar
  35. Manson LA (1991) Does antibody-dependent epitope masking permit progressive tumour growth in the face of cell-mediated cytotoxicity? Immunol Today 12: 352
    PubMed Google Scholar

Download references

Author information

Authors and Affiliations

  1. Section of Hematology and Oncology, Arizona Cancer Center, University of Arizona, 85724, Tucson, AZ, USA
    Cornelis J. A. Punt, Jose A. M. Barbuto, Hua Zhang & Evan M. Hersh
  2. Department of Biochemistry, Arizona Cancer Center, University of Arizona, 85724, Tucson, AZ, USA
    William J. Grimes
  3. Department of Obstetrics and Gynecology, University of Arizona, 85724, Tucson, AZ, USA
    Kenneth D. Hatch

Authors

  1. Cornelis J. A. Punt
    You can also search for this author inPubMed Google Scholar
  2. Jose A. M. Barbuto
    You can also search for this author inPubMed Google Scholar
  3. Hua Zhang
    You can also search for this author inPubMed Google Scholar
  4. William J. Grimes
    You can also search for this author inPubMed Google Scholar
  5. Kenneth D. Hatch
    You can also search for this author inPubMed Google Scholar
  6. Evan M. Hersh
    You can also search for this author inPubMed Google Scholar

Additional information

Work supported by grants from the Share and Concern Foundations and grant CA MOPP from the National Institutes of Health, C.J.A.P. is a visiting scientist from the University of Nijmegen, Department of Medical Oncology, Nijmegen, The Netherlands, and is supported by a Fulbright Senior Research Grant and grants from the Dutch Cancer Society and the Regional Cancer Center of the East Netherlands (IKO). J.A.M.B. is a visiting scientist from the University of Sao Paolo, Department of Immunology, Brazil, and is supported by grant 90/1844-4 from the FAPESP

Rights and permissions

About this article

Cite this article

Punt, C.J.A., Barbuto, J.A.M., Zhang, H. et al. Anti-tumor antibody produced by human tumor-infiltrating and peripheral blood B lymphocytes.Cancer Immunol Immunother 38, 225–232 (1994). https://doi.org/10.1007/BF01533513

Download citation

Key words