Skip to main content
NCBI home page
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1988 Sep;27(2):177–182. doi: 10.1007/BF00200024

In vitro generation of effector cells cytotoxic to autologous targets from chronic myeloid leukemia patients in remission

R Somasundaram 1, S G A Rao 2, S H Advani 1, Sudha G Gangal 1,✉
PMCID: PMC11038536  PMID: 3262014

Abstract

Peripheral blood lymphocytes (PBL) from chronic myeloid leukemia (CML) patients in remission were stimulated in vitro, in a 3-cell assay with autologous leukemic cells or autologous bone marrow (BM) cells alone, or each in combination with allogeneic PBL. The responder cells were used as effectors in a 4-h 51Cr release cytotoxicity assay using autologous targets such as leukemic cells, BM cells, phytohemagglutinin-induced lymphoblasts, and allogeneic K562 (erythroblastoid leukemic cell line) target cells. Sensitization of lymphocytes from CML patients with either autologous leukemic cells or BM cells generated cytotoxic cells (CTCs) capable of killing both the targets. These results suggested that in CML, the PBL may have been sensitized to myeloid maturation-related antigens in vivo, which, on secondary stimulation in vitro, may result in differentiation of CTCs cytotoxic to immature myeloid cells, either from autologous leukemic cells or autologous BM. The inability of PBL from patients with oral cancers to lyse autologous BM cells upon in vitro stimulation, supported this possibility. Clonogenic assays conducted to assess the colony forming potential of BM cells which had interacted with CTCs indicated that there was about 37% reduction in committed granulocyte stem cell colony formation without an appreciable change in committed granulocyte/monocyte stem cell units and clusters. Therefore, since the BM toxicity of the CTCs is not very high, these cells may have a potential clinical use in CML.

Keywords: Chronic Myeloid Leukemia, Bone Marrow Cell, Oral Cancer, Peripheral Blood Lymphocyte, Autologous Bone Marrow

References

  • 1.Bagby GC, Lawrence HJ, Neerhout RC. T lymphocyte — mediated granulopoietic failure. N Engl J Med. 1983;309:1073. doi: 10.1056/NEJM198311033091801. [DOI] [PubMed] [Google Scholar]
  • 2.Balsari A, Fossatti G, Taramelli D, Tona G, Delia D, Giardini R, Parmiani G. Allostimulation of patient lymphocytes generates both T and NK-like cells cytotoxic for autologous melanoma. Br J Cancer. 1985;52:73. doi: 10.1038/bjc.1985.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Burgess AW, Wilson EC, Metcalf D. Stimulation by human placental conditioned medium of haemopoietic colony forming human marrow cells. Blood. 1977;49:573. [PubMed] [Google Scholar]
  • 4.Dabholkar M, Advani S, Tatake R, Gangal S. Natural and antibody dependent cellular cytotoxicity in chronic myeloid leukemia patients in remission. Leuk Res. 1986;10:203. doi: 10.1016/0145-2126(86)90043-3. [DOI] [PubMed] [Google Scholar]
  • 5.Damle NK, Khare AG, Advani SH, Gangal SG. Leukemia associated in vitro cell mediated immunity in chronic myeloid leukemia patients in remission. Ind J Exp Biol. 1979;17:1376. [PubMed] [Google Scholar]
  • 6.DeVries J, Spitz H. Cloned human cytotoxic T lymphocyte (CTL) lines reactive with autologous melanoma cells. J Immunol. 1984;132:510. [PubMed] [Google Scholar]
  • 7.Grimm EA, Mazumdar A, Zhang HZ, Rosenberg SA. Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by IL-2-activated autologous human peripheral blood lymphocytes. J Exp Med. 1982;155:1823. doi: 10.1084/jem.155.6.1823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Herin M, Lemoine C, Weynants P, Vessiere F, VanPel A, Knuth A, Devos R, Boon T. Production of stable cytolytic T cell clones directed against autologous human melanoma. Int J Cancer. 1987;39:390. doi: 10.1002/ijc.2910390320. [DOI] [PubMed] [Google Scholar]
  • 9.Herrman F, Schmidt RE, Ritz J, Griffin JD. In vitro regulation of human hematopoiesis by natural killer cells: Analysis at a clonal level. Blood. 1987;69:246. [PubMed] [Google Scholar]
  • 10.Ichino Y, Ishikawa T. Generation of human cytotoxic T lymphocytes against fresh autologous and allogeneic solid tumors by mixed lymphocyte tumor cell culture with T cell growth factors. Gann. 1984;75:436. [PubMed] [Google Scholar]
  • 11.Khare AG, Advani SH, Gangal SG. In vitro generation of lymphocytoxicity to autochthonous leukemic cells in chronic myeloid leukemia. Br J Cancer. 1981;43:13. doi: 10.1038/bjc.1981.3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Kimura H, Yamaguchi Y, Fujisawa T. Cytotoxicity of autologous and allogeneic lymphocytes against cultured human lung cancer cells: Optimal conditions for the production of cytotoxic lymphocytes. Gann. 1984;75:1006. [PubMed] [Google Scholar]
  • 13.Lee SK, Oliver RT. Autologous leukemia specific T cell-mediated lymphocytotoxicity in patients with acute myelogenous leukemia. J Exp Med. 1978;147:912. doi: 10.1084/jem.147.3.912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Mazumdar A, Grimm EA, Rosenberg SA. Characterization of the lysis of fresh solid tumor by autologous lymphocytes activated in vitro with phytohemagglutinin. J Immunol. 1983;130:958. [PubMed] [Google Scholar]
  • 15.Rao SGA, Nadkarni KS, Joshi KS, Kothari VC, Advani SH. Normal responsiveness of granulocyte macrophage committed stem cells from patients with chronic myeloid leukemia to proliferation inhibition by prostaglandin E1. Ind J Exp Biol. 1984;22:340. [PubMed] [Google Scholar]
  • 16.Sondel PM, O'brien C, Porter L, Schlossman SF, Chess L. Cell mediated destruction of human leukemic cells by MHC identical lymphocytes: Requirement for a proliferative trigger in vitro. J Immunol. 1976;117:2197. [PubMed] [Google Scholar]
  • 17.Vanky F, Stjernsward J. In: Immunodiagnosis of cancer, part II. Herberman RB, McIntire KR, editors. New York: Marcel Dekker Inc; 1979. p. 998. [Google Scholar]
  • 18.Vanky F, Vose BM, Fopp M, Klein E. Human tumor lymphocyte interaction in vitro. IV. Specificity of primary and secondary autologous lymphocyte mediated cytotoxicity. J Natl Cancer Inst. 1979;62:1407. [PubMed] [Google Scholar]
  • 19.Vanky F, Argov S, Klein E. Tumor biopsy cells participating in systems in which cytotoxicity of lymphocytes is generated. Autologous and allogeneic studies. Int J Cancer. 1981;27:273. doi: 10.1002/ijc.2910270304. [DOI] [PubMed] [Google Scholar]
  • 20.Vose BM. Specific T cell mediated killing of autologous lung tumor cells. Cell Immunol. 1980;55:12. doi: 10.1016/0008-8749(80)90132-x. [DOI] [PubMed] [Google Scholar]
  • 21.Vose BM, Bonnard GD. Specific cytotoxicity against autologous tumor and proliferative response of human lymphocytes grown in interleukin-2. Int J Cancer. 1982;29:33. doi: 10.1002/ijc.2910290107. [DOI] [PubMed] [Google Scholar]
  • 22.Vose BM, Bonnard GD. Human tumor antigens defined by cytotoxicity and proliferative responses of cultured lymphoid cells. Nature. 1982;296:359. doi: 10.1038/296359a0. [DOI] [PubMed] [Google Scholar]
  • 23.Vose BM, Vanky F, Klein E. Lymphocyte cytotoxicity against autologous tumor biopsy cells in humans. Int J Cancer. 1977;20:512. doi: 10.1002/ijc.2910200407. [DOI] [PubMed] [Google Scholar]
  • 24.Zarling JM, Bach FH. Sensitization of lymphocytes against pooled allogeneic cells. I. Generation of cytotoxicity against autologous human lymphoblastoid cell lines. J Exp Med. 1978;147:1334. doi: 10.1084/jem.147.5.1334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Zarling JM, Bach FH. Continuous culture of T cells cytotoxic for autologous human leukemia cells. Nature. 1979;280:685. doi: 10.1038/280685a0. [DOI] [PubMed] [Google Scholar]
  • 26.Zarling JM, Raich PC, McKeough M, Bach FH. Generation of cytotoxic lymphocytes in vitro against autologous human leukemia cells. Nature. 1976;262:691. doi: 10.1038/262691a0. [DOI] [PubMed] [Google Scholar]
  • 27.Zarling JM, Robins HI, Raich PC, Bach FH, Bach ML. Generation of cytotoxic lymphocytes to autologous human leukemia cells by sensitization of pooled allogeneic normal cells. Nature. 1978;274:269. doi: 10.1038/274269a0. [DOI] [PubMed] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES