![]() ![]() Distal tumors actively responding to combination therapy demonstrated a phenotypic shift from regulatory T cell to Th1 in intratumoral CD4 + T cells, which was accompanied by a higher percentage of activated CD8 + T cells and higher IFNγ. Combination treatment also led to enhanced systemic antitumor immune responses capable of clearing distal intradermal tumors and controlling pulmonary metastasis. PD-L1 upregulation was found to be an acquired immune-resistance mechanism in the MB49 model, and the combination of VAX014 with systemic PD-L1 blockade resulted in a significant improvement in bladder tumor clearance rates and development of protective antitumor immunologic memory. ![]() Here, we demonstrated that the antitumor activity of VAX014 following IVE administration was dependent upon CD4 + and CD8 + T cells in two syngeneic orthotopic bladder tumor models (MB49 and MBT-2). VAX014 is a novel bacterial minicell-based, integrin-targeted oncolytic agent undergoing clinical investigation for intravesical (IVE) treatment of nonmuscle-invasive bladder cancer. Emerging clinical evidence indicates that the combination of local administration of immunotherapy with systemic immune-checkpoint blockade targeting the PD-1/PD-L1 pathway improves response rates in select solid tumor indications however, limited clinical experience with this approach exists in advanced bladder cancer patients. ![]()
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