Albumin-Flt3L Fusion Protein to Enhance Anti-Tumor Immunity and Antigen-specific T-cell Cytotoxicity

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Unmet Need: Active immunotherapy, such as anti-PD-1/PD-L1 and anti-CTLA-4 checkpoint blockage, involves the administration of molecules to mobilize host immune cells to recognize and kill tumors. Proper presentation of tumor antigens through antigen presenting cells is a prerequisite to elicit a potent immune response. Current strategies enhance antigen presentation by boosting conventional CD11b+ dendritic cells. While these are potent in antigen presentation, they perform subpar cross presentation. FMS-like tyrosine kinase 3 Ligand (Flt3L) is believed to expand CD8a+, CD103+, and Plasmacytoid dendritic cell subsets that have been shown to be effective at cross priming CD8+ cytotoxic T cells to promote anti-tumor activities; yet one drawback of Flt3L treatment is the need for daily injections due to its short half-life in vivo and its inability to target to the tumor location and the draining lymph nodes.



Technology Overview: Johns Hopkins researchers have generated a fusion protein between albumin and Flt3L (Alb-Flt3L) as a means to extend the cytokine’s half-life and promote trafficking to the lymphatic system. The fusion protein was shown potently expand cross priming dendritic cell populations in vivo following a single weekly injection, eliminating the need for daily injections of native Flt3L. In addition to exhibiting similar biological activity to the native Flt3L, the fusion protein can engender antigen specific T and B cell responses to OVA and HPV protein E7 long peptide immunizations. Hence, administering Alb-Flt3L in combination with additional chemotherapeutic agents, radiation therapy or immunotherapy is proposed as a promising new strategy to enhance therapeutic efficacy and improve patient outcome.


Stage of Development: The inventors have conducted pre-clinical research to evaluate the efficacy of their fusion protein in modulating immune cell phenotypes to promote anti-tumor immunity and antigen specific T cell responses. Alb-Flt3L appears to generate cross priming dendritic cell populations in vitro. The fusion protein also appears to extend the half-life of the cytokine versus the native protein and to target to the tumor location and the draining lymph node. In a mouse model of HPV-associated cancer, single weekly injections of the fusion protein reduced tumor burden and increased overall survival compared to control mice.


Inventors: T.C. Wu, Chien-Fu Hung, Brandon Lam


Patent Status: Pending Provisional application


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Vera Sampels
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