The comparative effects of IL-1 and TNF on AMN-anti-Ly 2.1 immunoconjugate therapy |
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Authors: | Kenia G Krauer Geoffrey A Pietersz |
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Institution: | (1) Austin Research Institute, Austin Hospital, 3084 Heidelberg, Victoria, Australia |
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Abstract: | The administration of mTNF and hIL-1 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 alone demonstrated a single 10 g iv injection produced 30% inhibition in tumor size while 3 doses of 1 g administered on alternative days produced 70% tumor inhibition. By contrast, hIL-1 was unable to significantly reduce E3 tumor size using single doses up to 10 g or a total of 30 g administered in 3 doses (iv or ip). However, intratumor injection of hIL-1 (20 g injected in 2 doses) produced 20% inhibition in tumor size. Combination therapy using AMN immunoconjugates with mTNF 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- whereas huIL-1 was without effect unless accompanying toxicity was seen. Clearly for this tumor, mTNF potentiated the effects of AMN immunoconjugates. Despite the shared biological properties of these cytokines, mTNF is superior to hIL- for augmenting drug immunoconjugate.Abbreviations AMN
Aminopterin
- CBF1
(C57BL6xBALB/c)F1 mice
- DMSO
Dimethyl sulfoxide
- E3
ITT(1)75NS E3
- HAMA
human-anti-mouse antibody
- i.p.
intraperitoneal(ly)
- I.T.
intratumor
- i.v.
intravenous(ly)
- hIL-1
recombinant human Interleukin-1-alpha
- MoAb
monoclonal antibody
- PBS
phosphate buffered saline
- SE
standard error
- s.c.
subcutaneous(ly)
- mTNF
recombinant murine tumor necrosis factor-alpha |
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Keywords: | IL-1 TNF drug immunoconjugates AMN Chemoimmunotherapy immunotoxin |
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