THE COMPARATIVE EFFECTS OF IL-1 AND TNF ON AMN-ANTI-LY 2.1 IMMUNOCONJUGATE THERAPY

The administration of mTNFalpha and hIL-1alpha was investigated for th eir potential to increase the anti-tumor activity of AMN-anti-Ly-2.1 a gainst the Ly-2.1+ murine thymoma ITT(1) 75 NS E3. Dose response studi es using mTNFalpha alone demonstrated a single 10 mug iv injection pro duced 30% inhibition in tumor size while 3 doses of 1 mug administered on alternative days produced 70% tumor inhibition. By contrast, hIL-1 alpha was unable to significantly reduce E3 tumor size using single do ses up to 10 mug or a total of 30 mug administered in 3 doses (iv or i p). However, intratumor injection of hIL-1alpha (20 mug injected in 2 doses) produced 20% inhibition in tumor size. Combination therapy usin g AMN immunoconjugates with mTNFalpha showed enhanced antitumor activi ty 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-1alpha was without effect. unless accompanying toxicity was seen. Clearly fo r this tumor, mTNFalpha potentiated the effects of AMN immunoconjugate s. Despite the shared biological properties of these cytokines, mTNFal pha is superior to hIL-alpha for augmenting drug immunoconjugate.