We have recently developed a skin genetic vaccine platform enabling local expression of xbp1/hsp70 and tumor Ag cDNA, which effectively controls tumor growth in a skin CD103+ DC-dependent, pDC-dependent and CD8+ T cell-dependent manner in diverse mouse tumor models.57 58 In the current report, we provide novel findings supporting the ability of this vaccine strategy to overcome tumor resistance to Brafi and/or PD1 checkpoint blockade in multifocal disease models of melanoma reflective of patients with multiple primary disease sites/disseminated disease. The gene discussed is XBP1; the disease is melanoma.