Role of vincristine in immunochemotherapy of leukemia in mouse or human models.
Synergistic antitumor effects between Vincristine (VCR) and allograft responses have been found in mice bearing allogeneic retrovirus-induced leukemia. In this model VCR depressed weakly allograft reactivity if given before but not after antigen administration. In a parallel human tumor model in vitro using HTLV-1 induced MT-2 leukemia, additive but not synergistic immuno-chemotherapeutic effects were obtained with allogeneic mononuclear cells (MNC) combined with VCR at 0.1 but not at 1 micrograms/ml. In this case natural immunity (NI) rather than antigen-dependent immunity (ADI) was involved in the combined effects of VCR + MNC. In the in vitro model pretreatment of effector cells with 1 or 0.1 micrograms/ml of VCR depressed natural cell-mediated cytotoxicity (NCMC). However when the drug was added to the effector + target cells during the 4 h cytotoxicity assay, 1 but not 0.1 micrograms/ml of the drug was capable of depressing NCMC function. These results would provide valuable information for developing in vitro immuno-chemotherapy studies in human tumor systems, including those characterized by the presence of tumor-associated oncogenic retroviruses, capable of depressing both NI and ADI functions.
Prete
S P
SP
Department of Experimental Medicine and Biochemical Sciences, II University of Rome, Italy.
De Filippi
R
R
Silvi
E
E
Bartocci
A
A
Giuliani
A
A
D000818:Animals; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007113:Immunity, Innate; D007167:Immunotherapy; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000637:transplantation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008979:Moloney murine leukemia virus; D014184:Transplantation, Homologous; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology; D014750:Vincristine / Q000627:therapeutic use*
D014750:Vincristine