Skip to main content
Journal of Cancer Research and Clinical Oncology logoLink to Journal of Cancer Research and Clinical Oncology
. 1983 Jan;105(1):83–93. doi: 10.1007/BF00391837

Immunotherapy of human leukemia with antibody to pluripotential K-562 stem cells

J Izquierdo 1, E R Robbio 1, B B Lozzio 2,, W Hanna 3,4
PMCID: PMC12253258  PMID: 6403549

Abstract

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.

Key words: Human leukemia, Pluripotent K-562 cells, Antibody, Immunotherapy

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

Footnotes

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

References

  1. 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 [DOI] [PubMed] [Google Scholar]
  2. Canelios GP (1977) The treatment of chronic granulocytic leukemia. Clin Haematol 6:113–128 [PubMed] [Google Scholar]
  3. 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 [DOI] [PubMed] [Google Scholar]
  4. 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 [DOI] [PubMed] [Google Scholar]
  5. Fukuda M (1980) K-562 human leukaemia cells express fetal type (i) antigen on different glycoproteins from circulating erythrocytes. Nature 285:405–407 [DOI] [PubMed] [Google Scholar]
  6. Fuhr JE, Bamberger EG, Lozzio CB, Lozzio BB (1981) Induction of hemoglobin synthesis in original K-562 cell line. Blood Cells 7:389–395 [PubMed] [Google Scholar]
  7. 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 [DOI] [PubMed] [Google Scholar]
  8. Gunz FW (1978) Towards a cure of acute granulocytic leukemia. Med J Aust 1:421–422 [DOI] [PubMed] [Google Scholar]
  9. Koffler HP, Billing R, Sparkes RS, Golde DW (1980) Antigens present on human myeloid leukemia cell lines. Leuk Res 4:69–77 [DOI] [PubMed] [Google Scholar]
  10. 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 [DOI] [PubMed] [Google Scholar]
  11. 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 [DOI] [PubMed] [Google Scholar]
  12. Laurell CB (1966) Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 15:45–52 [DOI] [PubMed] [Google Scholar]
  13. 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 [PubMed] [Google Scholar]
  14. 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 [Google Scholar]
  15. Lozzio BB, Lozzio CB (1979) Properties and usefulness of the original K-562 myelogenous leukemia cell line (Review). Leuk Res 3:363–370 [DOI] [PubMed] [Google Scholar]
  16. 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 [DOI] [PubMed] [Google Scholar]
  17. 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) [Google Scholar]
  18. 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 [Google Scholar]
  19. 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 [Google Scholar]
  20. 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 [Google Scholar]
  21. Lozzio CB, Lozzio BB (1975) Human chronic myelogenous leukemia cell line with positive Philadelphia chromosome. Blood 45:321–334 [PubMed] [Google Scholar]
  22. Mancini G, Carbonara AO, Heremans JF (1965) Immuno-chemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 2:235–254 [DOI] [PubMed] [Google Scholar]
  23. Motta R (1971) Passive immunotherapy of leukemia and other cancer. Adv Cancer Res 14:161–179 [DOI] [PubMed] [Google Scholar]
  24. 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 [Google Scholar]
  25. Pedersen B (1979) Spleen and relapse in chronic myeloid leukaemia. Scand J Haematol 22:369–374 [DOI] [PubMed] [Google Scholar]
  26. Rosenberg SA, Terry WS (1977) Passive immunotherapy of cancer in animals and man. Adv Cancer Res 25:323–388 [DOI] [PubMed] [Google Scholar]
  27. 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 [DOI] [PubMed] [Google Scholar]
  28. 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 [DOI] [PubMed] [Google Scholar]
  29. Wintrobe MM, Lee GR, Boggs DR, Bithell TC, Athens JW, Forester J (1974) Clinical hematology, 7th edn. Lea and Febiger, Philadelphia, p 1500 [Google Scholar]
  30. Wright PW, Hellstrom KE, Hellstrom IE, Bernstein ID (1976) Serotherapy of malignant disease. Med Clin North Am 60:607–621 [DOI] [PubMed] [Google Scholar]
  31. 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 [PubMed] [Google Scholar]

Articles from Journal of Cancer Research and Clinical Oncology are provided here courtesy of Springer

RESOURCES