Krauer K G, Pietersz G A
Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia.
Biotherapy. 1993;6(2):139-47. doi: 10.1007/BF01877427.
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.
研究了mTNFα和hIL-1α增强AMN-抗Ly-2.1对Ly-2.1 +小鼠胸腺瘤ITT(1) 75 NS E3的抗肿瘤活性的潜力。单独使用mTNFα的剂量反应研究表明，静脉注射单次10微克可使肿瘤大小抑制30%，而每隔一天注射3次1微克剂量可使肿瘤抑制70%。相比之下，hIL-1α使用高达10微克的单次剂量或分3次（静脉注射或腹腔注射）共给予30微克时，均无法显著减小E3肿瘤的大小。然而，瘤内注射hIL-1α（分2次注射20微克）可使肿瘤大小抑制20%。与单独使用每种药物相比，AMN免疫缀合物与mTNFα联合治疗显示出增强的抗肿瘤活性。生物分布研究表明，抗肿瘤活性是由于在mTNF-α存在下AMN免疫缀合物的定位增加（2至3倍），而huIL-1α除非出现伴随毒性否则没有效果。显然对于这种肿瘤，mTNFα增强了AMN免疫缀合物的作用。尽管这些细胞因子具有共同的生物学特性，但在增强药物免疫缀合物方面，mTNFα优于hIL-α。
