Summary
Gamma (γ) globulin was fractionated from the serum of a goat immunized with the pluripotential leukemia cell line K-562. The lyophilized γ-globulin preparation, termed leukoglobulin, contained about 50% immune IgG and suppressed the proliferation of heterotransplanted leukemia and lymphoma cells of human origin. The main aims of this study were to evaluate the potential therapeutic value of leukoglobulin and to determine its toxicity in humans with terminal leukemia and patients whose disease was unresponsive to current therapy. Two patients with CML, one with AMML, four with All, and one with AML were treated once a week for up to 5 weeks with leukoglobulin intravenously at doses ranging from 2 to 29 mg/kg. Leukoglobulin was well tolerated with minimal adverse effects and produced an initial mobilization of blasts from the bone marrow, spleen, and other organs with a parallel increase in the number of blasts in the systemic circulation. Subsequent injections of leukoglobulin led to a sharp decrease and the eventual eradication of blasts from the peripheral blood and bone marrow. Except in patients with CML, immature cells other than blasts also markedly diminished. The results of the clinical trials indicated a synergism with or potentiation of most chemotherapeutic agents used. Two possible uses for a combination of leukoglobulin and antileukemic drugs are indicated by the results were report here; drug-antibody synergism for cases showing no response to chemotherapy alone or leukoglobulin given immediately after chemotherapy is administered to eliminate residual leukemia cells. Alternatively, leukoglobulin can be given as a single therapeutic agent during the induction or maintenance phases of treatment to patients with leukemia resistant to other therapeutic combinations.
Similar content being viewed by others
Abbreviations
- CML:
-
chronic myelogenous leukemia
- AMML:
-
acute myelomonocytic leukemia
- ALL:
-
acute lymphoblastic leukemia
- AML:
-
acute myclogenous leukemia
- LAA:
-
leukemia-associated antigens
- IgG, IgA, IgM, IgD:
-
immunoglobulins G, A, M, and D
- i.v.:
-
intravenous
- BUN:
-
blood urea nitrogen
- BUS:
-
busulfan
- 6-MP:
-
6-mercaptopurine
- VCR:
-
vincristine
- DNM:
-
daunomycin
- PRED:
-
prednisone
- MTX:
-
methotrexate (amethopterin)
- CPM:
-
cyclophosphamide
- CIC:
-
cerebral intermittent claudication
- PBS:
-
phosphate-buffered saline
References
Bradfor M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Canelios GP (1977) The treatment of chronic granulocytic leukemia. Clin Haematol 6:113–128
Collins JL, Wust CJ, Lozzio BB, Lozzio CB (1977) Characterization of an antigen from the myelogenous leukemic cell line, K-562. J Natl Cancer Inst 59:1667–1674
Fialkow PJ, Jacobson RJ, Papayannopoulou T (1977) Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage. Am J Med 63:125–130
Fukuda M (1980) K-562 human leukaemia cells express fetal type (i) antigen on different glycoproteins from circulating erythrocytes. Nature 285:405–407
Fuhr JE, Bamberger EG, Lozzio CB, Lozzio BB (1981) Induction of hemoglobin synthesis in original K-562 cell line. Blood Cells 7:389–395
Fuhr JE, Bamberger EG, Lozzio CB, Lozzio BB, Felice AE, Altay G, Webber BB, Reese AI, Mayson SM, Huisman THJ (1982) Identification and quantitation of embryonic and three types of fetal hemoglobins produced on induction of the human pluripotent leukemia cell line K-562 with hemin. Am J Hematol 12:1–12
Gunz FW (1978) Towards a cure of acute granulocytic leukemia. Med J Aust 1:421–422
Koffler HP, Billing R, Sparkes RS, Golde DW (1980) Antigens present on human myeloid leukemia cell lines. Leuk Res 4:69–77
Latif ZA, Lozzio BB, Lozzio CB, Herberman RB, Wust CJ (1979) Abrogation of the proliferation of human leukemia cells in nude mice by an xenoantiserum. Leuk Res 3:371–378
Latif ZA, Lozzio BB, Wust CJ, Krauss S, Aggio MD, Lozzio CB (1980) Evaluation of drug-antibody conjugates in the treatment of human myelosarcomas transplanted in nude mice. Cancer 45:1326–1333
Laurell CB (1966) Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 15:45–52
Lozzio BB, Lozzio CB, Krauss S, Wust CJ, Girardi A (1977) Leukemia associated antigens detected by a non-human primate antiserum to a (Ph1+) myelogenous leukemic cell line. Blood 50:115–124
Lozzio BB (1979) Growth and treatment of human myelogenous leukemia in immunodeficient mice. In: Margison GP (ed) Advances in medical oncology research and education. Carcinogenesis, Vol. I. Pergamon Press, Oxford New York, pp 97–108
Lozzio BB, Lozzio CB (1979) Properties and usefulness of the original K-562 myelogenous leukemia cell line (Review). Leuk Res 3:363–370
Lozzio BB, Lozzio CB, Bamberger EG, Feliu AS (1981) A multipotential leukemia cell line (K-562) of human origin. Proc Soc Exp Biol Med 166:546–550
Lozzio BB, Lozzio CB, Ichiki AT, Kalmaz GD, Bamberger EG (1982a) K-562; A pluripotent leukemia stem cell line. In: Killmann SV-AA, Cronkite EP, Muller-Berat CN (eds) Haemopoietic stem cells. Munksgaard, Copenhagen (in press)
Lozzio BB, Machado E, Lozzio CB, Mitchell J, Wust CJ (1982b) Immunotherapy of metastases of human neoplastic cells grown in immunodeficient mice. Cancer Immunol Immunother 12:135–140
Lozzio BB, Lozzio CB, Machado EA, Wust CJ, Golde DW, Minowada J, Herbermann R (1982c) Suppression of the growth of hematopoietic malignant cells and their dissemination by an antibody to the K-562 pluripotential leukemia celline. In: Yohn David S, Blakeslee J (eds) Advances in comparative leukemia research. Elsevier/North Holland, Amsterdam New York, pp 593–595
Lozzio BB, Machado EA (1982) Transplantation and dissemination of hematopoietic malignancies in the nude and Lasat mice. In: Fogh J, Giovanella B (eds) The nude mouse in experimental and clinical research, vol. II. Academic Press, New York, pp 521–567
Lozzio CB, Lozzio BB (1975) Human chronic myelogenous leukemia cell line with positive Philadelphia chromosome. Blood 45:321–334
Mancini G, Carbonara AO, Heremans JF (1965) Immuno-chemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 2:235–254
Motta R (1971) Passive immunotherapy of leukemia and other cancer. Adv Cancer Res 14:161–179
Pedersen B (1977) Pathogenesis and blastic transformation of chronic myeloid leukemia as consequences of Ph1-positive stem cell hyperplasia: A unifying concept. Blood Cells 3:535–551
Pedersen B (1979) Spleen and relapse in chronic myeloid leukaemia. Scand J Haematol 22:369–374
Rosenberg SA, Terry WS (1977) Passive immunotherapy of cancer in animals and man. Adv Cancer Res 25:323–388
Ruggero D, Baccarani M, Gobbi M, Tura S (1979) Adult acute lymphoblastic leukemia study of 32 patients and analysis of prognostic factors. Scand J Haematol 22:154–164
Whitson ME, Lozzio CB, Lozzio BB, Wust CJ, Sonoda T, Avery B (1976) Cytotoxicity of antisera to a myelogenous leukemic cell line with the Philadelphia chromosome. J Natl Cancer Inst 56:903–907
Wintrobe MM, Lee GR, Boggs DR, Bithell TC, Athens JW, Forester J (1974) Clinical hematology, 7th edn. Lea and Febiger, Philadelphia, p 1500
Wright PW, Hellstrom KE, Hellstrom IE, Bernstein ID (1976) Serotherapy of malignant disease. Med Clin North Am 60:607–621
Wust CJ, Green M, Lozzio CB, Lozzio BB (1982) Antibody-dependent cytolysis of the leukemia cell line, K-562, in the absence of effector cells or complement. Blood 59:133–140
Author information
Authors and Affiliations
Additional information
These clinical trials were supported in part by the Fundación Roux-Ocefa, Buenos Aires, Argentina. The basic research was supported by Grants 18185 and 17533 awarded by the National Cancer Institute, DHHS, USA. The clinical trials have been approved by the Argentina Public Health Service (No. 22020000052098778/3) and by the University of Tennessee (CRP No. 878 and IRB No. 1445) National Cancer Institute Number 678, DHHS, USA Comp. of Tumor Immunotherapy Protocols 7:77, 1979
Rights and permissions
About this article
Cite this article
Izquierdo, J., Robbio, E.R., Lozzio, B.B. et al. Immunotherapy of human leukemia with antibody to pluripotential K-562 stem cells. J Cancer Res Clin Oncol 105, 83–93 (1983). https://doi.org/10.1007/BF00391837
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00391837