Enhancement of monoclonal antibody dependent cell mediated cytotoxicity by IL2 and GM‐CSF

摘要: Rodent monoclonal antibodies (MAb) directed against cells of the immune system may be used in vivo for applications including conditioning prior to marrow transplantation and treatment lymphoid malignancies. Although some MAb lyse targets by complement fixation, dependent cell mediated cytotoxicity (MAb-DCC) appears an important additional effector mechanism. We have investigated cellular basis phenomenon response recombinant cytokines attempt maximize efficacy MAb-DCC thereby increase therapeutic potency MAbs. Blood mononuclear (PBM) coated with CAMPATH 1G (pan lymphocyte reactive rat IgG2b) were as (T) autologous lymphocytes or granulocytes (E) cells. studied function normal donors well patients 1 week before 3-6 weeks after bone (BMT). In absence 1G, specific 51Cr release from PBM was less than 1% all groups, even pre-incubation granulocyte-macrophage, colony stimulating factor (GM-CSF) interleukin-2 (IL2). presence 5 micrograms/ml MAb, at E:T ratio 50:1, induced a low level (6.5%) auto rising 9% IL2 (P = 0.02). Granulocytes had greater activity inducing 10% 51CR (range 2-23%) which rose 21.6% GM-CSF 12-48%) 0.001). Pre-BMT, killing not significantly different normal, responded GM-CSF. contrast, granulocyte BMT impaired (51Cr 3%) showed no rise Killing lymphocytes, however, remained did their response. Loss coincided significant post-BMT impairment oxidative metabolism; expression Fc receptors II III, normal. Optimum effect is likely achieved when are given together appropriate cytokines, choice will depend upon clinical circumstances.