Intratumoral plasmid IL-12 electroporation therapy in advanced melanoma patients induces systemic and intratumoral T cell responses

Abstract

Whereas systemic IL-12 is associated with potentially life-threatening toxicity, intra-tumoral delivery of IL-12 through tavokinogene telseplasmid electroporation (tavo) is safe and can induce tumor regression at distant sites. The mechanism by which these responses are mediated is unknown, but is presumed to result from a cellular immune response. In a phase II clinical trial of tavo (NCT01502293), samples from 28 cutaneous melanoma patients with in-transit disease were assessed for immune responses induced with this treatment. Within the blood circulating immune cell population, we found that the frequencies of circulating PD-1+ CD4+ and CD8+ T cells declined with treatment. Circulating immune responses to gp100 were also detected following treatment as measured by IFN-γ ELISPOT. Patients with a greater antigen-specific circulating immune response also had higher numbers of CD8+ T cells within the tumor. Clinical response was also associated with increased intratumoral CD3+ T cells. Finally, intratumoral T cell clonality and convergence were increased after treatment, indicating a focusing of the TCR repertoire. These results indicated that local treatment with tavo can induce a systemic T cell response and recruit T cells to the tumor microenvironment.