Skip to main content
Log in

Initial experience with treatment of human B cell lymphoma with anti-CD19 monoclonal antibody

  • Original articles
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Summary

Six patients with progressive B cell non-Hodgkin's lymphoma have been treated with an IgG2a mouse monoclonal antibody (mAb) against the B cell differentiation antigen CD19, with total doses varying from 225 mg to 1000 mg. Free mAb was detected in the serum after doses of 15–30 mg. After the mAb infusions the number of circulating tumour cells was temporarily reduced, but in some cases antibody-coated cells remained in the circulation for several days. mAb penetrated to extravascular tumour sites; in general higher doses were required to saturate cells in the lymph nodes than to sensitize tumour cells in the bone marrow. mAb doses of up to 250 mg were given i.v. over 4 h without major toxicity. One patient twice achieved a partial remission after two periods of mAb treatment with an 8-month interval; the second remission lasted for 9 months. One patient showed a minor response. None of the patients made antibodies against the mouse immunoglobulin. Serum immunoglobulin levels were followed as a measure of the function of the normal B cell compartment; no significant changes were seen up to 6 months after mAb treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

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. Berinstein N, Levy R (1987) Treatment of a murine B cell lymphoma with monoclonal antibodies and IL 2. J Immunol 139: 971

    Google Scholar 

  2. Bertram JH, Gill PS, Levine AM, Boquiren D, Hoffman FM, Meyer P, Mitchell MS (1986) Monoclonal antibody T 101 in T cell malignancies: a clinical, pharmacokinetic, and immunologic correlation. Blood 69: 752

    Google Scholar 

  3. Brown SL, Miller RA, Homing SJ, Czerwinski D, Hart SM, McElderry R, Basham T, Warnke RA, Merigan TC, Levy R (1989) Treatment of B-cell lymphomas with anti-idiotype antibodies alone and in combination with alpha interferon. Blood 73: 651

    Google Scholar 

  4. De Rie MA, Zeijlemaker WP, Von dem Borne AEGKr (1988) Inhibition by vinca alkaloids and colchicine of antigenic modulation induced by anti-CD19 monoclonal antibodies. Leukemia Res 12: 135

    Google Scholar 

  5. De Rie MA, Schumacher TNM, Van Schijndel GMW, Van Lier RAW, Miedema F (1989) Regulatory role of CD19 molecules in B-cell activation and differentiation. Cell Immunol 118: 368

    Google Scholar 

  6. Dyer MJS, Hale G, Hayhoe FGJ, Waldmann H (1989) Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody isotype. Blood 73: 1431

    Google Scholar 

  7. Eisenthal A, Lafreniere R. Lefor AT, Rosenberg SA (1987) Effect of anti-B16 melanoma monoclonal antibody on established murine B16 melanoma liver metastases. Cancer Res 47: 2771

    Google Scholar 

  8. Fokkens WJ, Vroom ThM, Rijntjes E, Mulder PGH (1989) Fluctuation of the number of CD-1(T6)-positive dendritic cells, presumably Langerhans cells, in the nasal mucosa of patients with an isolated grass-pollen allergy before, during and after the grass-pollen season. J Allerg Clin Immunol 85: 39

    Google Scholar 

  9. Foon KA (1989) Biological response modifiers: the new immunotherapy. Cancer Res 49: 1621

    Google Scholar 

  10. Hale G, Clark MR, Marcus R, Winter G, Dyer MJS, Phillips JM, Riechmann L, Waldmann H (1984) Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody CAMPATH-1H. Lancet ii: 139

    Google Scholar 

  11. Harris DT, Mastrangelo MJ (1989) Serotherapy of cancer. Semin Oncol 16: 180

    Google Scholar 

  12. Honsik CJ, Jung G, Reisfeld RA (1986) Lymphokine-activated killer cells targeted by monoclonal antibodies to the disialogangliosides GD2 and GD3 specifically lyse human tumor cells of neuroectodermal origin. Proc Natl Acad Sci USA 83: 7893

    Google Scholar 

  13. Kawase I, Komuta K, Hara H, Inoue I, Hosoe S, Ikeda T, Shirasaka T, Yokota T, Tanio Y, Masuno T, Kishimoto S (1988) Combined therapy of mice bearing a lymphokine-activated killer-resistant tumor with recombinant interleukin-2 and an antitumor monoclonal antibody capable of inducing antibody-dependent cellular cytotoxicity. Cancer Res 48: 1173

    Google Scholar 

  14. Knapp W, Dörken B, Gilks WR, Rieber EP, Schmidt RE, Stein H, Von dem Borne AEGKr (eds) (1989) Leucocyte typing IV, 4th international workshop and conference on human leucocyte differentiation antigens, Vienna 1989, Oxford University Press, Oxford

    Google Scholar 

  15. Lowder JN, Meeker TC, Levy R (1985) Monoclonal antibody therapy of lymphoid malignancy. Cancer Surv 4: 359

    Google Scholar 

  16. Meeker TC, Lowder J, Maloney DG, Miller RA, Thielemans K, Warnke R, Levy R (1985) A clinical trial of anti-idiotype therapy for B cell malignancy. Blood 65: 1349

    Google Scholar 

  17. Morgan AC, Sullivan W, Graves S, Woodhouse CS (1989) Murine monoclonal IgG3 to human colorectal tumor-associated antigens: enhancement of antibody-dependent cell-mediated cytotoxicity by interleukin 2. Cancer Res 49: 2773

    Google Scholar 

  18. Munn DH, Cheung N-KV (1987) Interleukin-2 enhancement of monoclonal antibody-mediated cellular cytotoxicity against human melanoma. Cancer Res 47: 6600

    Google Scholar 

  19. Ortaldo JR, Woodhouse C, Morgan AC, Herberman RB, Cheresh DA, Reisfeld R (1987) Analysis of effector cells in human antibody-dependent cellular cytotoxicity with murine monoclonal antibodies. J Immunol 138: 3566

    Google Scholar 

  20. Pezzutto A, Dörken B, Rabinovitch PS, Ledbetter JA, Moldenhauer G, Clark EA (1987) CD19 monoclonal antibody HD37 inhibits anti-immunoglobulin-induced B cell activation and proliferation. J Immunol 138: 2793

    Google Scholar 

  21. Press OW, Appelbaum F, Ledbetter JA, Marin PJ, Zarlin J, Kidd P, Thomas ED (1987) Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas. Blood 69: 584

    Google Scholar 

  22. Press OW, Eary JF, Badger CC, Martin PJ, Appelbaum FR, Levy R, Miller R, Brown S, Nelp WB, Krohn KA, Fisher D, DeSanted K, Porter B, Kidd P, Thomas ED, Bernstein ID (1989) Treatment of refractory non-Hodgkin's lymphoma with radiolabeled MB-1 (anti-CD37) antibody. J Clin Oncol 7: 1027

    Google Scholar 

  23. Press OW, Farr AG, Borroz KI, Anderson SK, Martin PJ (1989) Endocytosis and degradation of monoclonal antibodies targeting human B cell malignancies. Cancer Res 49: 4906

    Google Scholar 

  24. Rankin EM, Hekman A (1984) Mouse monoclonal antibodies against the idiotype of human B cell non-Hodgkin lymphomas: production, characterization and use to monitor the progress of disease. Eur J Immunol 14: 1119

    Google Scholar 

  25. Rankin EM, Hekman A, Somers R, Ten Bokkel Huinink W (1985) Treatment of two patients with B cell lymphoma with monoclonal anti-idiotype antibodies. Blood 65: 1373

    Google Scholar 

  26. Shiloni E, Eisenthal A, Sachs D, Rosenberg SA (1987) Antibody—dependent cellular cytotoxicity mediated by murine lymphocytes activated in recombinant interleukin 2. J Immunol 138: 1992

    Google Scholar 

  27. Slaper-Cortenbach ICM, Admiraal LG, Van Leeuwen EF, Kerr JM, Von dem Borne AEGKr, Tetteroo PAT (1990) Effective purging of bone marrow by a combination of immunorosette depletion and complement lysis. Exp Hematol 18: 49

    Google Scholar 

  28. Uckun FM, Ledbetter JA (1988) Immunobiologic differences between normal and leukemic human B-cell precursors. Proc Natl Acad Sci USA 85: 8603

    Google Scholar 

  29. Uckun FM, Jaszcz W, Ambrus JL, Fauci AS, Gajl-Pecszalska K, Song CW, Wick MR, Myers DE, Waddick K, Ledbetter JA (1988) Detailed studies on expression and function of CD19 surface determinant by using B43 monoclonal antibody and the clinical potential of anti-CD19 immuno-toxins. Blood 71: 13

    Google Scholar 

  30. Vuist WMJ, Van Buitenen F, De Rie MA, Hekman A, Rümke P, Melief CJM (1989) Potentiation by interleukin-2 of Burkitt's lymphoma therapy with anti-pan B (anti-CD19) monoclonal antibodies in a mouse xeno-transplantation model. Cancer Res 49: 3783

    Google Scholar 

  31. WHO handbook for reporting results of cancer treatment. WHO Offset Publ. no 48, Geneva, WHO 1979

  32. Zola H (1987) The surface antigens of human B lymphocytes. Immunol Today 8: 308

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by the Dutch Cancer Society (grant NKI 84-14)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hekman, A., Honselaar, A., Vuist, W.M.J. et al. Initial experience with treatment of human B cell lymphoma with anti-CD19 monoclonal antibody. Cancer Immunol Immunother 32, 364–372 (1991). https://doi.org/10.1007/BF01741331

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01741331

Key words

Navigation