Susceptibility of Human Leukemia Cells to Allogeneic and Autologous Lymphokine-Activated Killer Cells and Its Augmentation by Exposure of Leukemia Target Cells to Cytotoxic Drugs In Vitro and In Vivo
Interleukin-2- (IL-2-)activated cytotoxic effector cells, known as lymphokine- activated killer (LAK) cells, lyse a wide variety of fresh solid tumor cells (Grimm et al. 1982; Itoh et al. 1986) as well as fresh noncultured leukemia cells (Oshimi et al. 1986; Lotzova et al. 1987; Fierro et al. 1988; Teichmann et al. 1989) in a fashion not restricted by the major histocompatibility complex (MHC). LAK cell cytotoxicity is predominantly mediated by CD3-/CD56+ activated natural killer (NK) cells and only to a small degree by MHC-unrestricted CD3+/CD56+ T cells (Phillips and Lanier 1986; Herberman et al. 1987; Tilden et al. 1987; Saito et al. 1988). Human leukemia cells possess a distinct LAK cell susceptibility which varies considerably in different subtypes of leukemia (Teichmann et al. 1992). Maximal cytolysis by activated effector cells is desirable for therapy. The current study therefore aimed at investigating whether in vitro exposure of leukemic cells to cytotoxic agents, relevant for leukemia treatment, can augment the susceptibility of fresh noncultured leukemia cells to LAK cell lysis. In addition, we also studied the susceptibility of leukemia cells both before and after exposure to cytotoxic drugs given in vivo during induction chemotherapy.
KeywordsToxicity Chromium Lymphoma Leukemia Oncol
Unable to display preview. Download preview PDF.
- Boyed AW, Dunn SM, Fecondo JV, Culvenor JG, Duehrsen U, Burns GF, Wawryk SO (1989) Regulation of expression of a human intercellular adhesion molecule (ICAM-1) during lymphohematopoietic differentiation. Blood 73: 1896–1903Google Scholar
- Dutcher JP, Creekmore S, Weiss GR, Margolin K, Markowitz AB, Roper M, Parkinson D, Ciobanu N, Fisher RI, Boldt DH, Doroshow JH, Rayner AA, Hawkins M, Atkins M (1989) A phase II study of interleukin-2 and lymphokine- activated killer cells in patients with metastatic malignant melanoma. J Clin Oncol 7: 477–485PubMedGoogle Scholar
- Fisher RI, Coltman CA, Doroshow JH, Rayner AA, Hawkins MJ, Mier JW, Wiernik P, McMannis JD, Weiss GR, Margolin KA, Gemlo BT, Hoth DF, Parkinson DR, Paietta E (1988) Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 108: 518–523PubMedGoogle Scholar
- Herberman RB, Hiserodt JC, Vujanovic N, Balch CM, Lotzova E, Bolhuis R, Golub S, Lanier LL, Phillips JH, Riccardi C, Ritz J, Santoni A, Schmidt RE, Uchida A (1987) Lymphokine-activated killer cell activity. Characteristics of effector cells and their progenitors in blood and spleen. Immunol Today 8: 178–181CrossRefGoogle Scholar
- Nagarkatti M, Nagarkatti PS, Kaplan AM (1988) Differential effects of BCNU on T cell, macrophage, natural killer and lymphokine-activated killer cell activities in mice bearing a syngeneic tumor. Caner Immunol Immunother 27: 38–46Google Scholar
- Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson C, White DE (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin- 2 alone. N Engl J Med 316: 889–897PubMedCrossRefGoogle Scholar
- Thiel E, Kranz BR, Raghavachar A, Bartram CR, Löffler H, Messerer D, Ganser A, Ludwig WD, Büchner T, Hoelzer D (1989) Prethymic phenotype and genotype of pre-T (CD 7+/ER-) — cell leukemia and its clinical significance within adult acute lymphoblastic leukemia. Blood 73: 1247–1258PubMedGoogle Scholar