The comparative effects of IL-1 and TNF on AMN-anti-Ly 2.1 immunoconjugate therapy.
The administration of mTNF alpha and hIL-1 alpha was investigated for their potential to increase the anti-tumor activity of AMN-anti-Ly-2.1 against the Ly-2.1+ murine thymoma ITT(1) 75 NS E3. Dose response studies using mTNF alpha alone demonstrated a single 10 micrograms iv injection produced 30% inhibition in tumor size while 3 doses of 1 microgram administered on alternative days produced 70% tumor inhibition. By contrast, hIL-1 alpha was unable to significantly reduce E3 tumor size using single doses up to 10 micrograms or a total of 30 micrograms administered in 3 doses (iv or ip). However, intratumor injection of hIL-1 alpha (20 micrograms injected in 2 doses) produced 20% inhibition in tumor size. Combination therapy using AMN immunoconjugates with mTNF alpha showed enhanced antitumor activity compared to each agent alone. Biodistribution studies revealed that anti-tumor activity, was due to increased localization (2-3 fold) of AMN immunoconjugates in the presence of mTNF-alpha whereas huIL-1 alpha was without effect unless accompanying toxicity was seen. Clearly for this tumor, mTNF alpha potentiated the effects of AMN immunoconjugates. Despite the shared biological properties of these cytokines, mTNF alpha is superior to hIL-alpha for augmenting drug immunoconjugate.
Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia.
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Krauer
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Pietersz
D000630:Aminopterin / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000950:Antigens, Ly / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004357:Drug Synergism; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013945:Thymoma / Q000628:therapy; D013953:Thymus Neoplasms / Q000628:therapy; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D000922:Immunotoxins; D007375:Interleukin-1; D007457:Iodine Radioisotopes; D014409:Tumor Necrosis Factor-alpha; D000630:Aminopterin