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 structurally well-characterized 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 various mouse models of cancer, single weekly injections of the fusion protein reduced tumor burden and increased overall survival compared to control mice.
An IND application can be reached within 18 months with appropriate funding.
Inventors: T.C. Wu, Chien-Fu Hung, Brandon Lam
