Concomitant treatment of MBT-2 bladder tumour by tumour necrosis factor alpha and interferon alpha in conjunction with delayed type hypersensitivity immunotherapy.
In our previous study [9], we reported the anti-tumour effect of TNF on mouse bladder tumour (MBT-2) both in vivo and in vitro. Inoculation of a single dose of TNF alone caused significant but transient tumour growth inhibition. Subsequent repeated doses of TNF did not sustain or augment the anti-tumour effect. The current experiments were undertaken to assess the anti-tumour activity of (i)-concomitant treatment of TNF-A and IFN-A against MBT-2 bladder tumour and (ii)-concomitant TNF + IFN-A treatment in conjunction with T-DTH (delayed-type hypersensitivity) immunotherapy. Systemic administration of multiple doses of TNF + IFN-A in vivo caused initial partial tumour regression followed by tumour growth inhibition up to 14 days following treatment. This combined treatment showed an enhanced anti-tumour effect compared to TNF-A treatment alone. Immunotherapy of MBT-2 tumour-bearing mice with T-DTH "immune" effector cells alone did not cause significant tumour growth inhibition. In contrast, concomitant administration of both T-DTH effector cells and TNF + IFN-A in MBT-2 tumour-bearing mice resulted in significant tumour growth inhibition for up to 16 days. The immune effector cells conferring immunotherapy were isolated from the spleens of tumour-immunized, "DTH-primed" animals and were characterized as Lyt 1+2- helper/DTH T cells (CD4+ phenotype). These cells mediate both DTH response to MBT-2 tumour antigens as well as anti-MBT-2 tumour protection. In vitro treatment of the "immune" cells with TNF-A resulted predominantly in the proliferation of Lyt 1+ T cells versus Lyt 2+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Surgery, University Hospital, University of Western Ontario, London, Canada.
S A
SA
Kadhim
J L
JL
Chin
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000628:therapy*; D003131:Combined Modality Therapy; D005200:FANFT; D005260:Female; D016219:Immunotherapy, Adoptive; D007370:Interferon Type I / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000628:therapy*
D007370:Interferon Type I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005200:FANFT