Pharmaceutical compositions activating LT-beta receptor for treating or reducing the advancement, severity or effects of neoplasia, method for selecting LT-beta receptor activating agent and antibodies against LT-beta receptor

摘要

The present invention relates to pharmaceutical compositions useful for activating LT-beta receptor signaling, which in turn elicits potent anti-proliferative effects on tumor cells. More particularly, this invention relates to lymphotoxin heteromeric complexes formed between lymphotoxin-alpha and multiple subunits of lymphotoxin-beta , which induce cytotoxic effects on tumor cells in the presence of lymphotoxin-beta receptor activating agents. Also within the scope of this invention are antibodies directed against the lymphotoxin-beta receptor, which act as lymphotoxin-beta receptor activating agents alone or in combination with other lymphotoxin-beta receptor activating agents either in the presence or in absence of lymphotoxin-alpha/beta complexes. A screening method for selecting such antibodies is provided. This invention also relates to compositions and methods using cross-linked anti-lymphotoxin-beta receptor antibodies either alone or in the presence of other lymphotoxin-beta receptor activating agents to potentiate tumor cell cytotoxicity.