Targeting of Stat-3 Signaling in the Hematopoietic System Evokes Multicomponent Therapeutic Antitumor Immunity

The immune system can act as an extrinsic suppressor of tumors. Therefore, tumor progression depends in part on mechanisms that down modulate intrinsic immune surveillance. Identifying these inhibitory pathways may provide promising targets to enhance antitumor immunity. Scientists at Johns Hopkins University and the University of Florida have shown that Stat3 is constitutively activated in diverse tumor-infiltrating immune cells, and ablating Stat3 in hematopoietic cells triggers an intrinsic immune-surveillance system that inhibits tumor growth and metastasis. They observed a markedly enhanced function of dendritic cells, T cells, natural killer (NK) cells and neutrophils in tumor-bearing mice with Stat3(-/-) hematopoietic cells, and showed that tumor regression requires immune cells. Targeting Stat3 with a small-molecule drug induces T cell- and NK cell-dependent growth inhibition of established tumors otherwise resistant to direct killing by the inhibitor. Their findings show that Stat3 signaling restrains natural tumor immune surveillance and that inhibiting hematopoietic Stat3 in tumor-bearing hosts elicits multicomponent therapeutic antitumor immunity. Description (Set) Proposed Use (Set) This invention demonstrates that agents that target Stat3 in the hematopoietic system will generate anti-tumor immunity even if these agents do not target Stat3 directly in the tumor. Additionally, this invention shows that agents that target Stat3 inhibitors such as siRNAs to hematopoietic elements rather than to the tumor will generate anti-tumor immunity. Finally, inhibitors of Stat3 could involve siRNAs, shRNAs or small molecules conjugated to ligands that bind receptors on hematopoietic cells such as (but not confined to) dendritic cells. Patent (Set) Published Patents: WO/2006/065894; US/2006/0127502

Inventor(s): Pardoll, Drew M.

Type of Offer: Licensing

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