Abstract: Improved methods for treating neoplastic diseases such as cancer are provided by using muteins of human tumor necrosis factor-alpha (TNF-?). Compared to wild-type human TNF-? these therapeutic TNF muteins have higher specific anti-tumor activity, but with much reduced systemic toxicity and milder side effects such chills and fever. In addition, potentially synergistic, novel combinations of the inventive TNF-? muteins with other anti-neoplastic agents are provided for effectively treating patients having particular types of cancer or malignancy or at particular stages of cancer development, and for mitigating resistance of the patients to treatment of non-TNF antineoplastic agents.

Abstract: Improved methods for treating neoplastic diseases such as cancer are provided by using muteins of human tumor necrosis factor-alpha (TNF-&agr;). Compared to wild-type human TNF-&agr; these therapeutic TNF muteins have higher specific anti-tumor activity, but with much reduced systemic toxicity and milder side effects such chills and fever. In addition, potentially synergistic, novel combinations of the inventive TNF-&agr; muteins with other anti-neoplastic agents are provided for effectively treating patients having particular types of cancer or malignancy or at particular stages of cancer development.